Molecular control of steady-state dendritic cell maturation and immune homeostasis

Annual Review of Immunology

Volumn 31, Issue , 2013, Pages 743-791

  Hammer, Gianna Elena ^a   Ma, Averil ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

A20; Autoimmunity; Colitis; Costimulatory molecules; MyD88; Toll like receptors

Indexed keywords

BETA CATENIN; BRUTON TYROSINE KINASE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CD209 ANTIGEN; FLT3 LIGAND; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR; INTERLEUKIN 10; INTERLEUKIN 6; LECTIN RECEPTOR; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MYELOID DIFFERENTIATION FACTOR 88; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN PROTEIN; PATTERN RECOGNITION RECEPTOR; RETINOIC ACID INDUCIBLE PROTEIN I; STAT1 PROTEIN; STAT3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR T BET; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 3; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6;

ADAPTIVE IMMUNITY; AUTOIMMUNE DISEASE; CELL CYCLE ARREST; CELL EXPANSION; CELL MIGRATION; COLITIS; DENDRITIC CELL; GENE OVEREXPRESSION; GLUCONEOGENESIS; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOGENICITY; IMMUNOLOGICAL TOLERANCE; INFLAMMATORY DISEASE; INNATE IMMUNITY; INTRACELLULAR SIGNALING; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SPONDYLARTHRITIS; STEADY STATE; UBIQUITINATION;

ANIMALS; CELL DIFFERENTIATION; DENDRITIC CELLS; HOMEOSTASIS; HUMANS; LECTINS, C-TYPE; MEMBRANE GLYCOPROTEINS; MICE; RECEPTORS, IMMUNOLOGIC; RECEPTORS, PATTERN RECOGNITION; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 84875537655     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-020711-074929     Document Type: Review

References (306)

1. Steinman RM, Cohn ZA. 1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137(5):1142-62
2. Nobel Assem. Karolinska Inst. 2011. The gatekeepers of the immune system. 2011 Nobel Prize in Physiology or Medicine: Popular Information, 8 pp. http://www.nobelprize.org/nobel-prizes/medicine/laureates/2011/ popular-medicineprize2011.pdf
3. Steinman RM. 2012. Decisions about dendritic cells: past, present, and future. Annu. Rev. Immunol. 30:1-22
4. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, et al. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767-811
5. Cresswell P. 1994. Assembly, transport, and function of MHC class II molecules. Annu. Rev. Immunol. 12:259-93
6. Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, et al. 2000. Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288(5465):522-27
7. Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I. 2003. Activation of lysosomal function during dendritic cell maturation. Science 299(5611):1400-3
8. Greenwald RJ, Freeman GJ, Sharpe AH. 2005. The B7 family revisited. Annu. Rev. Immunol. 23:515-48
9. Kamath AT, Pooley J, O'Keeffe MA, Vremec D, Zhan Y, et al. 2000. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165(12):6762-70
10. Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, et al. 2000. Developmental control of endocytosis in dendritic cells by Cdc42. Cell 102(3):325-34
11. Reis e Sousa C. 2006. Dendritic cells in a mature age. Nat. Rev. Immunol. 6(6):476-83
12. Fujii S-I, Liu K, SmithC, Bonito AJ, Steinman RM. 2004. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J. Exp. Med. 199(12):1607-18
13. Sato A, Iwasaki A. 2004. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proc. Natl. Acad. Sci. USA 101(46):16274-79
14. Nolte MA, Leibundgut-Landmann S, Joffre O, Reis e Sousa C. 2007. Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo. J. Exp.Med. 204(6):1487-501
15. + T cell populations lacking helper function. Nat. Immunol. 6(2):163-70
16. Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, et al. 2007. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27(4):610-24
17. Rimoldi M, Chieppa M, Larghi P, Vulcano M, Allavena P, Rescigno M. 2005. Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. Blood 106(8):2818-26
18. Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140(6):805-20
19. Kawasaki T, Kawai T, Akira S. 2011. Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol. Rev. 243(1):61-73
20. Iwasaki A, Medzhitov R. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5(10):987-95
21. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. 1996. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86(6):973-83
22. Poltorak A, He X, Smirnova I, LiuMY, Van Huffel C, et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396):2085-88
23. Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi G-P, et al. 2008. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 456(7222):658-62
24. Kagan JC, Su T, HorngT, Chow A, Akira S, Medzhitov R. 2008.TRAMcouples endocytosis ofToll-like receptor 4 to the induction of interferon-β. Nat. Immunol. 9(4):361-68
25. Barbalat R, Ewald SE, Mouchess ML, BartonGM. 2011. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 29:185-214
26. Fukui R, Saitoh S-I, Kanno A, Onji M, Shibata T, et al. 2011. Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking. Immunity 35(1):69-81
27. Mouchess ML, Arpaia N, Souza G, Barbalat R, Ewald SE, et al. 2011. Transmembrane mutations in Toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. Immunity 35(5):721-32
28. Moresco EMY, LaVine D, Beutler B. 2011. Toll-like receptors. Curr. Biol. 21(13):R488-93
29. Zaru R, Ronkina N, Gaestel M, Arthur JSC, Watts C. 2007. The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways. Nat. Immunol. 8(11):1227-35
30. Kaisho T, Tanaka T. 2008. Turning NF-κB and IRFs on and off in DC. Trends Immunol. 29(7):329-36
31. Asselin-Paturel C, Trinchieri G. 2005. Production of type I interferons: plasmacytoid dendritic cells and beyond. J. Exp. Med. 202(4):461-65
32. Asselin-Paturel C, Brizard G, Chemin K, Boonstra A, O'Garra A, et al. 2005. Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J. Exp. Med. 201(7):1157-67
33. Gay NJ, Gangloff M, Weber ANR. 2006. Toll-like receptors as molecular switches. Nat. Rev. Immunol. 6(9):693-98
34. Hou B, Reizis B, DeFranco AL. 2008. Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms. Immunity 29(2):272-82
35. Haley K, Igyártó BZ, Ortner D, Bobr A, Kashem S, et al. 2012. Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration. J. Immunol. 188(9):4334-39
36. HouW-S, Van Parijs L. 2004. A Bcl-2-dependent molecular timer regulates the life span and immunogenicity of dendritic cells. Nat. Immunol. 5(6):583-89
37. Chen M, Huang L, Wang J. 2007. Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity. Blood 109(10):4360-67
38. Li X, Jiang S, Tapping RI. 2010. Toll-like receptor signaling in cell proliferation and survival. Cytokine 49(1):1-9
39. Fuertes Marraco SA, Scott CL, Bouillet P, Ives A, Masina S, et al. 2011. Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by PolyIC in vivo. PLoS ONE 6(6):e20189
40. Zanoni I, Ostuni R, Capuano G, ColliniM, Caccia M, et al. 2009. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature 460(7252):264-68
41. West MA, Wallin RPA, Matthews SP, SvenssonHG, Zaru R, et al. 2004. Enhanced dendritic cell antigen capture via Toll-like receptor-induced actin remodeling. Science 305(5687):1153-57
42. Xu Y, Jagannath C, Liu X-D, Sharafkhaneh A, Kolodziejska KE, Eissa NT. 2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27(1):135-44
43. Shi C-S, Kehrl JH. 2008. MyD88 and TRIF target Beclin 1 to trigger autophagy in macrophages. J. Biol. Chem. 283(48):33175-82
44. DelgadoMA, Elmaoued RA, Davis AS, Kyei G, Deretic V. 2008. Toll-like receptors control autophagy. EMBO J. 27(7):1110-21
45. Shi C-S, Kehrl JH. 2010. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci. Signal. 3(123):ra42
46. Into T, Inomata M, Takayama E, Takigawa T. 2012. Autophagy in regulation of Toll-like receptor signaling. Cell Signal. 24(6):1150-62
47. Blander JM, Medzhitov R. 2004. Regulation of phagosome maturation by signals from Toll-like receptors. Science 304(5673):1014-18
48. Blander JM, Medzhitov R. 2006. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440(7085):808-12
49. Blander JM, Medzhitov R. 2006. On regulation of phagosomematuration and antigen presentation. Nat. Immunol. 7(10):1029-35
50. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. 2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118(2):229-41
51. Marshak-Rothstein A, Rifkin IR. 2007. Immunologically active autoantigens: the role of Toll-like receptors in the development of chronic inflammatory disease. Annu. Rev. Immunol. 25:419-41
52. Kaisho T, Takeuchi O, Kawai T, Hoshino K, Akira S. 2001. Endotoxin-induced maturation of MyD88-deficient dendritic cells. J. Immunol. 166(9):5688-94
53. Walton KLW, He J, Kelsall BL, Sartor RB, Fisher NC. 2006. Dendritic cells in germ-free and specific pathogen-free mice have similar phenotypes and in vitro antigen presenting function. Immunol. Lett. 102(1):16-24
54. Wilson NS, YoungLJ, Kupresanin F, Naik SH, Vremec D, et al. 2008. Normal proportion and expression of maturation markers inmigratory dendritic cells in the absence of germs orToll-like receptor signaling. Immunol. Cell Biol. 86(2):200-5
55. Shortman K, Liu Y-J. 2002. Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2(3):151-61
56. Deane JA, Pisitkun P, Barrett RS, Feigenbaum L, Town T, et al. 2007. Control of Toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 27(5):801-10
57. Tian J, Avalos AM, Mao S-Y, Chen B, Senthil K, et al. 2007. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat. Immunol. 8(5):487-96
58. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang Y-H, et al. 2007. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564-69
59. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, et al. 2009. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 206(9):1983-94
60. Sadanaga A, Nakashima H, AkahoshiM, Masutani K, Miyake K, et al. 2007. Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. Arthritis Rheum. 56(5):1618-28
61. Silver KL, Crockford TL, Bouriez-Jones T, Milling S, Lambe T, Cornall RJ. 2007. MyD88-dependent autoimmune disease in Lyn-deficient mice. Eur. J. Immunol. 37(10):2734-43
62. Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ. 2010. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity 33(6):967-78
63. Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, et al. 2011. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat. Immunol. 12(12):1184-93
64. Slack E, Hapfelmeier S, Stecher B, Velykoredko Y, Stoel M, et al. 2009. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325(5940):617-20
65. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, et al. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2(4):361-67
66. Niess JH, Brand S, Gu X, Landsman L, Jung S, et al. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307(5707):254-58
67. Chieppa M, Rescigno M, Huang AYC, Germain RN. 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp.Med. 203(13):2841-52
68. Foligne B, Zoumpopoulou G, Dewulf J, Ben Younes A, Chareyre F, et al. 2007. A key role of dendritic cells in probiotic functionality. PLoS ONE 2(3):e313
69. Arques JL, Hautefort I, Ivory K, Bertelli E, Regoli M, et al. 2009. Salmonella induces flagellin-and MyD88-dependent migration of bacteria-capturing dendritic cells into the gut lumen. Gastroenterology 137(2):579-87.e2
70. +, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J. Exp. Med. 206(13):3101-14
71. Hall JA, Bouladoux N, SunC-M, WohlfertEA, BlankRB, et al. 2008. CommensalDNAlimits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29(4):637-49
72. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, et al. 2008. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455(7216):1109-13
73. Buzás EI, György B, Pásztoi M, Jelinek I, Falus A, Gabius H-J. 2006. Carbohydrate recognition systems in autoimmunity. Autoimmunity 39(8):691-704
74. Garci-Vallejo JJ, vanKooykY. 2009. Endogenous ligands forC-type lectin receptors: the true regulators of immune homeostasis. Immunol. Rev. 230(1):22-37
75. Sancho D, Reis e Sousa C. 2012. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu. Rev. Immunol. 30:491-529
76. Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, et al. 2000. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12(1):71-81
77. + dendritic cells to the marginal zone of mouse spleen. Proc. Natl. Acad. Sci. USA 106(5):1524-29
78. Steinman RM, Nussenzweig MC. 2002. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA 99(1):351-58
79. Burgdorf S, Kautz A, Bóhnert V, Knolle PA, Kurts C. 2007. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 316(5824):612-16
80. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, et al. 2007. Differential antigen processing by dendritic cell subsets in vivo. Science 315(5808):107-11
81. + T cells by targeting antigens to human dendritic cells through DCIR. Blood 116(10):1685-97
82. Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, et al. 2011. ComparableThelper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc. Natl. Acad. Sci. USA 108(6):2384-89
83. Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, et al. 2007. BDCA2/Fc-RIγ complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 5(10):e248
84. Ráock J, Schneider E, Grán JR, Grützkau A, Káuppers R, et al. 2007. CD303 (BDCA-2) signals in plasmacytoid dendritic cells via a BCR-like signalosome involving Syk, Slp65 and PLCγ2. Eur. J. Immunol. 37(12):3564-75
85. van Vliet SJ, Paessens LC, Broks-van den BergVCM, Geijtenbeek TBH, vanKooyk Y. 2008. TheC-type lectin macrophage galactose-type lectin impedes migration of immature APCs. J. Immunol. 181(5):3148-55
86. Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garci-Vallejo JJ, et al. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol. Immunol. 46(6):1240-49
87. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, et al. 2001. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194(6):769-79
88. Zhang J, Somani AK, Siminovitch KA. 2000. Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling. Semin. Immunol. 12(4):361-78
89. Kaneko T, Saito Y, Kotani T, Okazawa H, Iwamura H, et al. 2012. Dendritic cell-specific ablation of the protein tyrosine phosphatase SHP1 promotes Th1 cell differentiation and induces autoimmunity. J. Immunol. 188(11):5397-407
90. Croker BA, Lawson BR, Rutschmann S, Berger M, Eidenschenk C, et al. 2008. Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. Proc. Natl. Acad. Sci. USA 105(39):15028-33
91. + dendritic cells but not by Langerhans cells. Science 301(5641):1925-28
92. Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E, et al. 2003. Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19(1):47-57
93. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA, et al. 2006. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25(1):153-62
94. + T cells after viral stimulation. PLoS ONE 3(2):e1691
95. Young LJ, Wilson NS, Schnorrer P, Proietto A, ten Broeke T, et al. 2008. Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat. Immunol. 9(11):1244-52
96. + T cells. Nat. Immunol. 8(10):1060-66
97. Ariizumi K, Shen GL, Shikano S, Xu S, Ritter R, et al. 2000. Identification of a novel, dendritic cellassociated molecule, dectin-1, by subtractive cDNA cloning. J. Biol. Chem. 275(26):20157-67
98. van Vliet SJ, Gringhuis SI, Geijtenbeek TBH, van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectinMGLwith CD45. Nat. Immunol. 7(11):1200-8
99. Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, et al. 2005. Selective probiotic bacteria induce IL-10-producing regulatoryTcells in vitro bymodulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115(6):1260-67
100. Bron PA, van BaarlenP, Kleerebezem M. 2012. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat. Rev. Microbiol. 10(1):66-78
101. Zhou Y, Kawasaki H, Hsu S-C, Lee RT, Yao X, et al. 2010. Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. Nat. Med. 16(10):1128-33
102. Saunders SP, Barlow JL, Walsh CM, Bellsoi A, Smith P, et al. 2010. C-type lectin SIGN-R1 has a role in experimental colitis and responsiveness to lipopolysaccharide. J. Immunol. 184(5):2627-37
103. Heinsbroek SE, Oei A, Roelofs JJTH, Dhawan S, te Velde A, et al. 2012. Genetic deletion of dectin-1 does not affect the course of murine experimental colitis. BMC Gastroenterol. 12:33
104. Sancho D, Joffre OP, Keller AM, Rogers NC, Martáez D, et al. 2009. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458(7240):899-903
105. Ahrens S, Zelenay S, Sancho D, Hanč P, KjóS, et al. 2012. F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36(4):635-45
106. Zelenay S, Keller AM, Whitney PG, Schraml BU, Deddouche S, et al. 2012. The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virusinfected mice. J. Clin. Investig. 122(5):1615-27
107. Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. 2008. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat. Immunol. 9(10):1179-88
108. Fujikado N, Saijo S, Yonezawa T, Shimamori K, Ishii A, et al. 2008. Dcir deficiency causes development of autoimmune disease in mice due to excess expansion of dendritic cells. Nat. Med. 14(2):176-80
109. + T cells. Ann. Rheum. Dis. 67(12):1742-49
110. + T cells. PLoS Pathog. 6(11):e1001188
111. Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, Stern AC, Vellenga E. 1989. Correction of granulocytopenia in Felty's syndrome by granulocyte- macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood 74(8):2769-70
112. Xu WD, Firestein GS, Taetle R, Kaushansky K, Zvaifler NJ. 1989. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J. Clin. Investig. 83(3):876-82
113. Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. 1998. Protection from collageninduced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J. Immunol. 161(7):3639-44
114. Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. 2001. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res. 3(5):293-98
115. Sonderegger I, Iezzi G, MaierR, Schmitz N, KurrerM, Kopf M. 2008.GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J. Exp. Med. 205(10):2281-94
116. Vremec D, Lieschke GJ, Dunn AR, Robb L, Metcalf D, Shortman K. 1997. The influence of granulocyte/macrophage colony-stimulating factor on dendritic cell levels in mouse lymphoid organs. Eur. J. Immunol. 27(1):40-44
117. Greter M, Helft J, Chow A, Hashimoto D, Mortha A, et al. 2012. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity 36(6):1031-46
118. Meyer-Wentrup F, Benitez-Ribas D, Tacken PJ, Punt CJA, Figdor CG, et al. 2008. Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-α production. Blood 111(8):4245-53
119. Meyer-Wentrup F, Cambi A, Joosten B, Looman MW, de Vries IJM, et al. 2009. DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production. J. Leukoc. Biol. 85(3):518-25
120. Gmez CP, Tiemi ShioM, Duplay P, OlivierM, Descoteaux A. 2012. The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. J. Immunol. 189(5):2203-10
121. Lorentzen JC, Flornes L, Ekĺw C, Báckdahl L, RibbhammarU, et al. 2007. Association of arthritis with a gene complex encoding C-type lectin-like receptors. Arthritis Rheum. 56(8):2620-32
122. Franchi L, Muñoz-Planillo R, Náñez G. 2012. Sensing and reacting to microbes through the inflammasomes. Nat. Immunol. 13(4):325-32
123. Rathinam VAK, Vanaja SK, Fitzgerald KA. 2012. Regulation of inflammasome signaling. Nat. Immunol. 13(4):333-32
124. Davis BK, Wen H, Ting JP-Y. 2011. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 29:707-35
125. Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, et al. 2012. NLRC4-driven production of IL-1βdiscriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol. 13(5):449-56
126. Biswas A, Petnicki-Ocwieja T, Kobayashi KS. 2012. NOD2: a key regulator linking microbiota to intestinal mucosal immunity. J. Mol. Med. 90(1):15-24
127. StroberW, Watanabe T. 2011. NOD2, an intracellular innate immune sensor involved in host defense and Crohn's disease. Mucosal Immunol. 4(5):484-95
128. Maeda S, Hsu L-C, Liu H, Bankston LA, Iimura M, et al. 2005. Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1βprocessing. Science 307(5710):734-38
129. Watanabe T, Kitani A, Murray PJ, Wakatsuki Y, Fuss IJ, StroberW. 2006. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulatedTLR2signaling and induction of antigen-specific colitis. Immunity 25(3):473-85
130. Watanabe T, Asano N, Murray PJ, Ozato K, Tailor P, et al. 2008. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J. Clin. Investig. 118(2):545-59
131. Petnicki-Ocwieja T, Hrncir T, Liu Y-J, Biswas A, Hudcovic T, et al. 2009. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl. Acad. Sci. USA 106(37):15813-18
132. Macho Fernandez E, Valenti V, Rockel C, Hermann C, Pot B, et al. 2011. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 60(8):1050-59
133. Cooney R, Baker J, Brain O, Danis B, Pichulik T, et al. 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16(1):90-97
134. Penack O, SmithOM, Cunningham-Bussel A, Liu X, RaoU, et al. 2009.NOD2regulates hematopoietic cell function during graft-versus-host disease. J. Exp. Med. 206(10):2101-10
135. Holler E, Rogler G, Brenmoehl J, Hahn J, Herfarth H, et al. 2006. Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination. Blood 107(10):4189-93
136. Holler E, Hahn J, Andreesen R, Rogler G, Brenmoehl J, et al. 2008. NOD2/CARD15 polymorphisms in allogeneic stem-cell transplantation from unrelated donors: T depletion matters. J. Clin. Oncol. 26(2):338-39
137. Chen M, Wang Y-H, Wang Y, Huang L, Sandoval H, et al. 2006. Dendritic cell apoptosis in the maintenance of immune tolerance. Science 311(5764):1160-64
138. Stranges PB, Watson J, Cooper CJ, Choisy-Rossi C-M, Stonebraker AC, et al. 2007. Elimination of antigen-presenting cells and autoreactive T cells by Fas contributes to prevention of autoimmunity. Immunity 26(5):629-41
139. Park D, Lapteva N, Seethammagari M, Slawin KM, Spencer DM. 2006. An essential role for Akt1 in dendritic cell function and tumor immunotherapy. Nat. Biotechnol. 24(12):1581-90
140. Birnberg T, Bar-On L, Sapoznikov A, Caton ML, Cervantes-Barragán L, et al. 2008. Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29(6):986-97
141. Ohnmacht C, Pullner A, King SBS, Drexler I, Meier S, et al. 2009. Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J. Exp. Med. 206(3):549-59
142. + T cell subsets. Immunity 31(5):811-22
143. Kang S-J, Liang H-E, Reizis B, Locksley RM. 2008. Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells. Immunity 29(5):819-33
144. Marrack P, Kappler J. 1997. Positive selection of thymocytes bearing αβT cell receptors. Curr. Opin. Immunol. 9(2):250-55
145. Ladi E, Schwickert TA, Chtanova T, Chen Y, Herzmark P, et al. 2008. Thymocyte-dendritic cell interactions near sources of CCR7 ligands in the thymic cortex. J. Immunol. 181(10):7014-23
146. Le Borgne M, Ladi E, Dzhagalov I, Herzmark P, Liao YF, et al. 2009. The impact of negative selection on thymocyte migration in the medulla. Nat. Immunol. 10(8):823-30
147. HadeibaH, LahlK, Edalati A, OderupC, Habtezion A, et al. 2012. Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36(3):438-50
148. Li J, Park J, Foss D, Goldschneider I. 2009. Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus. J. Exp. Med. 206(3):607-22
149. Henri S, Vremec D, Kamath A, Waithman J, Williams S, et al. 2001. The dendritic cell populations of mouse lymph nodes. J. Immunol. 167(2):741-48
150. Wilson NS, El-Sukkari D, Belz GT, Smith CM, Steptoe RJ, et al. 2003. Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood 102(6):2187-94
151. Banchereau J, Pascual V, Palucka AK. 2004. Autoimmunity through cytokine-induced dendritic cell activation. Immunity 20(5):539-50
152. + T cell regulatory functions. J. Immunol. 178(1):271-79
153. Ding D, MehtaH, McCuneWJ, Kaplan MJ. 2006. Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J. Immunol. 177(9):5878-89
154. + T cell tolerance and permits effective immunity. Immunity 29(6):934-46
155. + T cells. Nat. Immunol. 2(11):1010-17
156. Merad M, Ginhoux F, Collin M. 2008. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8(12):935-47
157. Merad M, Manz MG. 2009. Dendritic cell homeostasis. Blood 113(15):3418-27
158. Reizis B. 2010. Regulation of plasmacytoid dendritic cell development. Curr. Opin. Immunol. 22(2):206-11
159. Liu K, Nussenzweig MC. 2010. Origin and development of dendritic cells. Immunol. Rev. 234(1):45-54
160. Shortman K, Naik SH. 2007. Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 7(1):19-30
161. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, et al. 2009. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31(3):502-12
162. Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, et al. 2008. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135(1):37-48
163. + dendritic cells. Immunity 9(6):839-47
164. + dendritic cells in cytotoxic T cell immunity. Science 322(5904):1097-100
165. Ouaaz F, Arron J, Zheng Y, Choi Y, Beg AA. 2002. Dendritic cell development and survival require distinct NF-κB subunits. Immunity 16(2):257-70
166. Speirs K, Lieberman L, Caamano J, Hunter CA, Scott P. 2004. Cutting edge: NF-κB2 is a negative regulator of dendritic cell function. J. Immunol. 172(2):752-56
167. Wang J, Wang X, Hussain S, Zheng Y, Sanjabi S, et al. 2007. Distinct roles of different NF-κB subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells. J. Immunol. 178(11):6777-88
168. Macagno A, Napolitani G, Lanzavecchia A, Sallusto F. 2007. Duration, combination and timing: the signal integration model of dendritic cell activation. Trends Immunol. 28(5):227-33
169. van der Horst A, Burgering BMT. 2007. Stressing the role of FoxO proteins in life span and disease. Nat. Rev. Mol. Cell Biol. 8(6):440-50
170. Calnan DR, Brunet A. 2008. The FoxO code. Oncogene 27(16):2276-88
171. Dejean AS, Beisner DR, Ch'en IL, Kerdiles YM, Babour A, et al. 2009. Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nat. Immunol. 10(5):504-13
172. Fallarino F, Bianchi R, Orabona C, Vacca C, Belladonna ML, et al. 2004. CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice. J. Exp. Med. 200(8):1051-62
173. Orabona C, Grohmann U, Belladonna ML, Fallarino F, Vacca C, et al. 2004. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat. Immunol. 5(11):1134-42
174. Leach DR, KrummelMF, Allison JP. 1996. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271(5256):1734-36
175. Karandikar NJ, Vanderlugt CL, Walunas TL, Miller SD, Bluestone JA. 1996. CTLA-4: a negative regulator of autoimmune disease. J. Exp. Med. 184(2):783-88
176. Lin L, Hron JD, Peng SL. 2004. Regulation of NF-κB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a. Immunity 21(2):203-13
177. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, et al. 2004. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303(5666):2011-15
178. Rosas M, Dijkers PF, Lindemans CL, Lammers J-WJ, Koenderman L, Coffer PJ. 2006. IL-5-mediated eosinophil survival requires inhibition of GSK-3 and correlates with β-catenin relocalization. J. Leukoc. Biol. 80(1):186-95
179. Kastenbauer S, Ziegler-Heitbrock HW. 1999. NF-κB1 (p50) is upregulated in lipopolysaccharide tolerance and can block tumor necrosis factor gene expression. Infect. Immun. 67(4):1553-59
180. Dissanayake D, Hall H, Berg-Brown N, Elford AR, Hamilton SR, et al. 2011. Nuclear factor-κB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells. Nat. Med. 17(12):1663-67
181. Leung BP, Conacher M, Hunter D, McInnes IB, Liew FY, Brewer JM. 2002. A novel dendritic cellinduced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation. J. Immunol. 169(12):7071-77
182. ErikssonU, Ricci R, Hunziker L, KurrerMO, Oudit GY, et al. 2003. Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat. Med. 9(12):1484-90
183. Georgiev M, Agle LMA, Chu JL, Elkon KB, Ashany D. 2005. Mature dendritic cells readily break tolerance in normal mice but do not lead to disease expression. Arthritis Rheum. 52(1):225-38
184. Martin DA, Zhang K, Kenkel J, Hughes G, Clark E, et al. 2007. Autoimmunity stimulated by adoptively transferred dendritic cells is initiated by both αβand γ∞T cells but does not require MyD88 signaling. J. Immunol. 179(9):5819-28
185. + T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity. J. Exp. Med. 186(12):2057-62
186. Hamilton-Williams EE, Lang A, Benke D, Davey GM, Wiesmüller K-H, Kurts C. 2005. Cutting edge: TLR ligands are not sufficient to break cross-tolerance to self-antigens. J. Immunol. 174(3):1159-63
187. O'Keeffe M, Grumont RJ, Hochrein H, Fuchsberger M, Gugasyan R, et al. 2005. Distinct roles for the NF-κB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals. Blood 106(10):3457-64
188. ArtisD, Kane CM, Fiore J, Zaph C, Shapira S, et al. 2005. Dendritic cell-intrinsic expression of NF-κB1 is required to promote optimal Th2 cell differentiation. J. Immunol. 174(11):7154-59
189. Melli K, Friedman RS, MartinAE, Finger EB, Miao G, et al. 2009. Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues. J. Immunol. 182(5):2590-600
190. Mercurio F, DiDonato JA, Rosette C, Karin M. 1993. p105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction. Genes Dev. 7(4):705-18
191. Waterfield MR, Zhang M, Norman LP, Sun SC. 2003. NF-κB1/p105 regulates lipopolysaccharidestimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. Mol. Cell 11(3):685-94
192. Saccani S, Pantano S, Natoli G. 2003. Modulation of NF-κB activity by exchange of dimers. Mol. Cell 11(6):1563-74
193. Tong X, Yin L, Washington R, Rosenberg DW, Giardina C. 2004. The p50-p50 NF-κB complex as a stimulus-specific repressor of gene activation. Mol. Cell Biochem. 265(1-2):171-83
194. Carmody RJ, Ruan Q, Palmer S, Hilliard B, Chen YH. 2007. Negative regulation of Toll-like receptor signaling by NF-κB p50 ubiquitination blockade. Science 317(5838):675-78
195. Sha WC, LiouHC, Tuomanen EI, BaltimoreD. 1995. Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses. Cell 80(2):321-30
196. Cao S, Zhang X, Edwards JP, MosserDM. 2006. NF-κB1 (p50) homodimers differentially regulate proand anti-inflammatory cytokines in macrophages. J. Biol. Chem. 281(36):26041-50
197. Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ. 2004. Molecular mechanisms of interleukin-10-mediated inhibition of NF-κB activity: a role for p50. Clin. Exp. Immunol. 135(1):64-73
198. GarrettWS, LordGM, Punit S, Lugo-VillarinoG, Mazmanian SK, et al. 2007. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131(1):33-45
199. Garrett WS, Punit S, Gallini CA, MichaudM, Zhang D, et al. 2009. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16(3):208-19
200. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, et al. 2010. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8(3):292-300
201. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, et al. 2006. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25(2):309-18
202. Hapfelmeier S, Máuller AJ, Stecher B, Kaiser P, Barthel M, et al. 2008. Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in ∞invG S. Typhimurium colitis. J. Exp. Med. 205(2):437-50
203. Feng T, Wang L, Schoeb TR, Elson CO, Cong Y. 2010. Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J. Exp. Med. 207(6):1321-32
204. Farmer MA, Sundberg JP, Bristol IJ, Churchill GA, Li R, et al. 2001. A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice. Proc. Natl. Acad. Sci. USA 98(24):13820-25
205. Ermann J, Garrett WS, Kuchroo J, Rourida K, Glickman JN, et al. 2011. Severity of innate immunemediated colitis is controlled by the cytokine deficiency-induced colitis susceptibility-1 (Cdcs1) locus. Proc. Natl. Acad. Sci. USA 108(17):7137-41
206. Trombetta ES, Mellman I. 2005. Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 23:975-1028
207. Faure-AndráG, VargasP, YuseffM-I, HeuzáM, Diaz J, et al. 2008. Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. Science 322(5908):1705-10
208. Cresswell P. 1996. Invariant chain structure and MHC class II function. Cell 84(4):505-7
209. Lámmermann T, Bader BL, Monkley SJ, Worbs T, Wedlich- Sóldner R, et al. 2008. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453(7191):51-55
210. Shin J-S, EbersoldM, Pypaert M, Delamarre L, Hartley A, Mellman I. 2006. Surface expression ofMHC class II in dendritic cells is controlled by regulated ubiquitination. Nature 444(7115):115-18
211. Matsuki Y, Ohmura-Hoshino M, Goto E, Aoki M, Mito-Yoshida M, et al. 2007. Novel regulation of MHC class II function in B cells. EMBO J. 26(3):846-54
212. Walseng E, FurutaK, Bosch B, Weih KA, Matsuki Y, et al. 2010. Ubiquitination regulatesMHCclass IIpeptide complex retention and degradation in dendritic cells. Proc.Natl. Acad. Sci. USA 107(47):20465-70
213. Ma JK, PlattMY, Eastham-Anderson J, Shin J-S, Mellman I. 2012.MHCclass II distribution in dendritic cells and B cells is determined by ubiquitin chain length. Proc. Natl. Acad. Sci. USA 109(23):8820-27
214. Coscoy L, Ganem D. 2003. PHD domains and E3 ubiquitin ligases: viruses make the connection. Trends Cell Biol. 13(1):7-12
215. Thibodeau J, Bourgeois-Daigneault M-C, HupṕG, Tremblay J, Aumont A, et al. 2008. Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. Eur. J. Immunol. 38(5):1225-30
216. Jabbour M, Campbell EM, Fares H, Lybarger L. 2009. Discrete domains ofMARCH1mediate its localization, functional interactions, and posttranscriptional control of expression. J. Immunol. 183(10):6500-12
217. Ohmura-Hoshino M, Matsuki Y, Mito-Yoshida M, Goto E, Aoki-Kawasumi M, et al. 2009. Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. 183(11):6893-97
218. Baravalle G, Park H, McSweeney M, Ohmura-Hoshino M, Matsuki Y, et al. 2011. Ubiquitination of CD86 is a key mechanism in regulating antigen presentation by dendritic cells. J. Immunol. 187(6):2966-73
219. Al-Daccak R, Mooney N, Charron D. 2004. MHC class II signaling in antigen-presenting cells. Curr. Opin. Immunol. 16(1):108-13
220. + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity. Proc. Natl. Acad. Sci. USA 109(23):9059-64
221. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. 2000. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat. Immunol. 1(4):311-16
222. Kajino K, Nakamura I, Bamba H, Sawai T, Ogasawara K. 2007. Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation. Immunology 120(1):28-37
223. Abdi K, Singh NJ, Matzinger P. 2012. Lipopolysaccharide-activated dendritic cells: "exhausted" or alert and waiting? J. Immunol. 188(12):5981-89
224. Kobayashi K, Hernandez LD, Galán JE, Janeway CA, Medzhitov R, Flavell RA. 2002. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110(2):191-202
225. Foster SL, Hargreaves DC, Medzhitov R. 2007. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447(7147):972-78
226. Liu X, Zhan Z, Li D, Xu L, Ma F, et al. 2011. Intracellular MHC class II molecules promote TLRtriggered innate immune responses bymaintaining activation of the kinase Btk. Nat. Immunol. 12(5):416-24
227. Wahl MI, Fluckiger AC, Kato RM, Park H, Witte ON, Rawlings DJ. 1997. Phosphorylation of two regulatory tyrosine residues in the activation of Bruton's tyrosine kinase via alternative receptors. Proc. Natl. Acad. Sci. USA 94(21):11526-33
228. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, et al. 2003. Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J. Biol. Chem. 278(28):26258-64
229. Josefowicz SZ, Lu L-F, Rudensky AY. 2012. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30:531-64
230. Belkaid Y, Tarbell K. 2009. Regulatory T cells in the control of host-microorganism interactions. Annu. Rev. Immunol. 27:551-89
231. Darrasse-Jéze G, Deroubaix S, Mouquet H, Victora GD, Eisenreich T, et al. 2009. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 206(9):1853-62
232. Bar-On L, Birnberg T, Kim K-W, Jung S. 2010. Dendritic cell-restricted CD80/86 deficiency results in peripheral regulatory T-cell reduction but is not associated with lymphocyte hyperactivation. Eur. J. Immunol. 41:291-98
233. Seneschal J, Clark RA, Gehad A, Baecher-Allan CM, Kupper TS. 2012. Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 36(5):873-84
234. +CD44hi cells. Immunity 29(5):758-70
235. Hall JA, Grainger JR, Spencer SP, Belkaid Y. 2011. The role of retinoic acid in tolerance and immunity. Immunity 35(1):13-22
236. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, et al. 1992. Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature 359(6397):693-99
237. Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA. 2006. Transforming growth factor-βregulation of immune responses. Annu. Rev. Immunol. 24:99-146
238. Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, et al. 2007. Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449(7160):361-65
239. + regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J. Exp. Med. 204(8):1757-64
240. + dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205(9):2139-49
241. + regulatory T cells via integrin αvβ8. Gastroenterology 141(5):1802-12
242. Li MO, Sanjabi S, Flavell RA. 2006. Transforming growth factor-β controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25(3):455-71
243. Zhang N, Bevan MJ. 2012. TGF-β signaling to T cells inhibits autoimmunity during lymphopeniadriven proliferation. Nat. Immunol. 13(7):667-73
244. Melton AC, Bailey-Bucktrout SL, Travis MA, Fife BT, Bluestone JA, Sheppard D. 2010. Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J. Clin. Investig. 120(12):4436-44
245. Mellor AL, Munn DH. 2004. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4(10):762-74
246. Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F, et al. 2002. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. 3(11):1097-101
247. Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML, et al. 2011. Indoleamine 2, 3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol. 12(9):870-78
248. Mellor AL, Baban B, Chandler P, Marshall B, Jhaver K, et al. 2003. Cutting edge: induced indoleamine 2, 3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol. 171(4):1652-55
249. Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez RM, et al. 2010. Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329(5993):849-53
250. Denning TL, Wang Y-C, Patel SR, Williams IR, Pulendran B. 2007. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat. Immunol. 8(10):1086-94
251. Park S-J, Nakagawa T, Kitamura H, Atsumi T, Kamon H, et al. 2004. IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J. Immunol. 173(6):3844-54
252. Lunz JG, Specht SM, Murase N, Isse K, Demetris AJ. 2007. Gut-derived commensal bacterial products inhibit liver dendritic cellmaturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity. Hepatology 46(6):1946-59
253. Máuller M, Fink K, Geisel J, Kahl F, Jilge B, et al. 2008. Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. PLoS ONE 3(6):e2376
254. Kitamura H, KamonH, Sawa S-I, Park S-J, KatunumaN, et al. 2005. IL-6-STAT3 controls intracellular MHC class II αβdimer level through cathepsin S activity in dendritic cells. Immunity 23(5):491-502
255. Murray PJ. 2007. The JAK-STAT signaling pathway: input and output integration. J. Immunol. 178(5):2623-29
256. Káhn R, Láohler J, Rennick D, Rajewsky K, Máuller W. 1993. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263-74
257. Melillo JA, Song L, Bhagat G, Blazquez AB, Plumlee CR, et al. 2010. Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function. J. Immunol. 184(5):2638-45
258. Alexander WS, Hilton DJ. 2004. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu. Rev. Immunol. 22:503-29
259. Hanada T, Yoshida H, Kato S, Tanaka K, Masutani K, et al. 2003. Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity 19(3):437-50
260. Shen L, Evel-Kabler K, Strube R, Chen S-Y. 2004. Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity. Nat. Biotechnol. 22(12):1546-53
261. Evel-KablerK, SongX-T, Aldrich M, HuangXF, Chen S-Y. 2006.SOCS1restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. J. Clin. Investig. 116(1):90-100
262. Hong B, Ren W, Song X-T, Evel-Kabler K, Chen S-Y, Huang XF. 2009. Human suppressor of cytokine signaling 1 controls immunostimulatory activity of monocyte-derived dendritic cells. Cancer Res. 69(20):8076-84
263. Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, et al. 2002. SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17(5):583-91
264. Baetz A, FreyM, Heeg K, Dalpke AH. 2004. Suppressor of cytokine signaling (SOCS) proteins indirectly regulate Toll-like receptor signaling in innate immune cells. J. Biol. Chem. 279(52):54708-15
265. Mansell A, Smith R, Doyle SL, Gray P, Fenner JE, et al. 2006. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediatingMal degradation. Nat. Immunol. 7(2):148-55
266. Morita Y, Naka T, Kawazoe Y, Fujimoto M, Narazaki M, et al. 2000. Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts. Proc. Natl. Acad. Sci. USA 97(10):5405-10
267. + dendritic cell subset. Int. Immunol. 17(9):1167-78
268. Tezuka H, Abe Y, Asano J, Sato T, Liu J, et al. 2011. Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction. Immunity 34(2):247-57
269. + dendritic cells. J. Exp. Med. 208(10):2005-16
270. SeitzHM, Camenisch TD, LemkeG, EarpHS, Matsushima GK. 2007. Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J. Immunol. 178(9):5635-42
271. LemkeG, Burstyn-Cohen T. 2010. TAM receptors and the clearance of apoptotic cells. Ann. N. Y. Acad. Sci. 1209:23-29
272. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MBA, Lemke G. 2007. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131(6):1124-36
273. Sen P, Wallet MA, Yi Z, Huang Y, Henderson M, et al. 2007. Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-κB activation in dendritic cells. Blood 109(2):653-60
274. WalletMA, Sen P, Flores RR, Wang Y, Yi Z, et al. 2008. MerTK is required for apoptotic cell-induced T cell tolerance. J. Exp. Med. 205(1):219-32
275. Yi Z, Li L, Matsushima GK, Earp HS, Wang B, Tisch R. 2009. A novel role for c-Src and STAT3 in apoptotic cell-mediated MerTK-dependent immunoregulation of dendritic cells. Blood 114(15):3191-98
276. Lu Q, Lemke G. 2001. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293(5528):306-11
277. Gohlke PR, Williams JC, Vilen BJ, Dillon SR, Tisch R, Matsushima GK. 2009. The receptor tyrosine kinase MerTK regulates dendritic cell production of BAFF. Autoimmunity 42(3):183-97
278. Suh C-H, Hilliard B, Li S, Merrill JT, Cohen PL. 2010. TAM receptor ligands in lupus: protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus. Arthritis Res. Ther. 12(4):R146
279. Lee EG, Boone DL, Chai S, Libby SL, Chien M, et al. 2000. Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science 289(5488):2350-54
280. Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, et al. 2004. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature 430(7000):694-99
281. BooneDL, Turer EE, Lee EG, Ahmad R-C, Wheeler MT, et al. 2004. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat. Immunol. 5(10):1052-60
282. Hitotsumatsu O, Ahmad R-C, Tavares R, Wang M, Philpott D, et al. 2008. The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2 triggered signals. Immunity 28(3):381-90
283. Tavares RM, Turer EE, Liu CL, Advincula R, Scapini P, et al. 2010. The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity 33(2):181-91
284. Kool M, van Loo G, Waelput W, De Prijck S, Muskens F, et al. 2011. The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity 35(1):82-96
285. Evans PC, Ovaa H, Hamon M, Kilshaw PJ, Hamm S, et al. 2004. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity. Biochem. J. 378(Pt. 3):727-34
286. Bosanac I, Wertz IE, Pan B, Yu C, Kusam S, et al. 2010. Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling. Mol. Cell 40(4):548-57
287. Shembade N, Ma A, Harhaj EW. 2010. Inhibition of NF-κB signaling by A20 through disruption of ubiquitin enzyme complexes. Science 327(5969):1135-39
288. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ. 2011. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol. Cell 44(4):559-71
289. Song HY, Rothe M, Goeddel DV. 1996. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-κB activation. Proc. Natl. Acad. Sci. USA 93(13):6721-25
290. Heyninck K, Van Huffel S, Kreike M, Beyaert R. 2004. Yeast two-hybrid screening for proteins interacting with the anti-apoptotic protein A20. Methods Mol. Biol. 282:223-41
291. Verstrepen L, Verhelst K, van Loo G, Carpentier I, Ley SC, Beyaert R. 2010. Expression, biological activities and mechanisms of action of A20 (TNFAIP3). Biochem. Pharmacol. 80(12):2009-20
292. Vereecke L, Sze M, Mc Guire C, Rogiers B, Chu Y, et al. 2010. Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J. Exp. Med. 207(7):1513-23
293. CatonML, Smith-RaskaMR, Reizis B. 2007. Notch-RBP-J signaling controls the homeostasis of CD8-dendritic cells in the spleen. J. Exp. Med. 204(7):1653-64
294. Naik SH, Metcalf D, vanNieuwenhuijze A, Wicks I, WuL, et al. 2006. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat. Immunol. 7(6):663-71
295. Kato M, Sanada M, Kato I, Sato Y, Takita J, et al. 2009. Frequent inactivation ofA20 in B-cell lymphomas. Nature 459(7247):712-16
296. Schmitz R, Hansmann M, Bohle V, Martin-Subero J, Hartmann S, et al. 2009. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J. Exp. Med. 206:981-89
297. Wu H-J, Ivanov II, Darce J, Hattori K, Shima T, et al. 2010. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815-27
298. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85
299. Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, et al. 2008. Homeostatic MyD88-dependent signals cause lethal inflammation in the absence of A20. J. Exp. Med. 205(2):451-64
300. Melis L, Elewaut D. 2009. Progress in spondylarthritis. Immunopathogenesis of spondyloarthritis: Which cells drive disease? Arthritis Res. Ther. 11(3):233
301. Gaston H. 2006. Mechanisms of disease: the immunopathogenesis of spondyloarthropathies. Nat. Clin. Pract. Rheumatol. 2(7):383-92
302. Armaka M, Apostolaki M, Jacques P, Kontoyiannis DL, Elewaut D, Kollias G. 2008. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J. Exp. Med. 205(2):331-37
303. Kontoyiannis D, Boulougouris G, Manoloukos M, Armaka M, Apostolaki M, et al. 2002. Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease. J. Exp. Med. 196(12):1563-74
304. Keller C, Webb A, Davis J. 2003. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann. Rheum. Dis. 62(12):1128-32
305. Milia AF, Ibba-Manneschi L, Manetti M, Benelli G, Generini S, et al. 2011. Evidence for the prevention of enthesitis in HLA-B27/hβ2m transgenic rats treated with a monoclonal antibody against TNF-α. J. Cell. Mol. Med. 15(2):270-79
306. Taurog JD. 2010. The role of HLA-B27 in spondyloarthritis. J. Rheumatol. 37(12):2606-16