Functional specialization of skin dendritic cell subsets in regulating T cell responses

Frontiers in Immunology

Volumn 6, Issue OCT, 2015, Pages

  Clausen, Björn E ^a   Stoitzner, Patrizia ^b  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Contact hypersensitivity; Cross presentation; Dendritic cells; Immunotherapy; Infectious skin disease; Langerhans cells; Langerin; Skin cancer

Indexed keywords

GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERFERON REGULATORY FACTOR; INTERLEUKIN 17; INTERLEUKIN 6; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA1;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ARTICLE; CANCER IMMUNOTHERAPY; CANDIDA ALBICANS; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTACT ALLERGY; CROSS PRESENTATION; DENDRITIC CELL; DOWN REGULATION; HUMAN; NEOPLASM; NONHUMAN; PHENOTYPE; REGULATORY T LYMPHOCYTE; SKIN DISEASE; SKIN LEISHMANIASIS; TUMOR GROWTH; UPREGULATION;

EID: 84946563295     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00534     Document Type: Article

References (234)

1. Malissen B, Tamoutounour S, Henri S. The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol (2014) 14(6):417-28. doi:10.1038/nri3683.
2. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol (2013) 31:563-604. doi:10.1146/annurev-immunol-020711-074950.
3. Scott CL, Henri S, Guilliams M. Mononuclear phagocytes of the intestine, the skin, and the lung. Immunol Rev (2014) 262(1):9-24. doi:10.1111/imr.12220.
4. Iram N, Mildner M, Prior M, Petzelbauer P, Fiala C, Hacker S, et al. Age-related changes in expression and function of toll-like receptors in human skin. Development (2012) 139(22):4210-9. doi:10.1242/dev.083477.
5. Lebre MC, van der Aar AM, van Baarsen L, van Capel TM, Schuitemaker JH, Kapsenberg ML, et al. Human keratinocytes express functional toll-like receptor 3, 4, 5, and 9. J Invest Dermatol (2007) 127(2):331-41. doi:10.1038/sj.jid.5700530.
6. Miller LS, Modlin RL. Toll-like receptors in the skin. Semin Immunopathol (2007) 29(1):15-26. doi:10.1007/s00281-007-0061-8.
7. Tan S, Roediger B, Weninger W. The role of chemokines in cutaneous immunosurveillance. Immunol Cell Biol (2015) 93(4):337-46. doi:10.1038/icb.2015.16.
8. Ebner S, Ehammer Z, Holzmann S, Schwingshackl P, Forstner M, Stoitzner P, et al. Expression of c-type lectin receptors by subsets of dendritic cells in human skin. Int Immunol (2004) 16(6):877-87. doi:10.1093/intimm/dxh088.
9. Gregorio J, Meller S, Conrad C, Di Nardo A, Homey B, Lauerma A, et al. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med (2010) 207(13):2921-30. doi:10.1084/jem.20101102.
10. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med (2009) 361(5):496-509. doi:10.1056/NEJMra0804595.
11. Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol (2011) 29:163-83. doi:10.1146/annurev-immunol-031210-101345.
12. Nishibu A, Ward BR, Jester JV, Ploegh HL, Boes M, Takashima A. Behavioral responses of epidermal langerhans cells in situ to local pathological stimuli. J Invest Dermatol (2006) 126(4):787-96. doi:10.1038/sj.jid.5700107.
13. Ouchi T, Kubo A, Yokouchi M, Adachi T, Kobayashi T, Kitashima DY, et al. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome. J Exp Med (2011) 208(13):2607-13. doi:10.1084/jem.20111718.
14. Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. EMBO J (2014) 33(10):1104-16. doi:10.1002/embj.201488027.
15. Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z, Zwirner J, et al. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity (2004) 21(2):279-88. doi:10.1016/j.immuni.2004.06.014.
16. Tang A, Amagai M, Granger LG, Stanley JR, Udey MC. Adhesion of epidermal langerhans cells to keratinocytes mediated by e-cadherin. Nature (1993) 361(6407):82-5. doi:10.1038/361082a0.
17. Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, et al. Disruption of e-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity (2007) 27(4):610-24. doi:10.1016/j.immuni.2007.08.015.
18. Mellman I, Clausen BE. Immunology. Beta-catenin balances immunity. Science (2010) 329(5993):767-9. doi:10.1126/science.1194185.
19. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature (1998) 392(6673):245-52. doi:10.1038/32588.
20. Hemmi H, Yoshino M, Yamazaki H, Naito M, Iyoda T, Omatsu Y, et al. Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells. Int Immunol (2001) 13(5):695-704. doi:10.1093/intimm/13.5.695.
21. Weinlich G, Heine M, Stössel H, Zanella M, Stoitzner P, Ortner U, et al. Entry into afferent lymphatics and maturation in situ of migrating murine cutaneous dendritic cells. J Invest Dermatol (1998) 110(4):441-8. doi:10.1046/j.1523-1747.1998.00161.x.
22. Wilson NS, Young LJ, Kupresanin F, Naik SH, Vremec D, Heath WR, et al. Normal proportion and expression of maturation markers in migratory dendritic cells in the absence of germs or toll-like receptor signaling. Immunol Cell Biol (2008) 86(2):200-5. doi:10.1038/sj.icb.7100125.
23. Probst HC, Lagnel J, Kollias G, van den Broek M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity (2003) 18(5):713-20. doi:10.1016/S1074-7613(03)00120-1.
24. Spörri R, Reise Sousa C. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol (2005) 6(2):163-70. doi:10.1038/ni1162.
25. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol (2003) 21:685-711. doi:10.1146/annurev.immunol.21.120601.141040.
26. Waithman J, Allan RS, Kosaka H, Azukizawa H, Shortman K, Lutz MB, et al. Skin-derived dendritic cells can mediate deletional tolerance of class i-restricted self-reactive T cells. J Immunol (2007) 179(7):4535-41. doi:10.4049/jimmunol.179.7.4535.
27. Hochweller K, Wabnitz GH, Samstag Y, Suffner J, Hämmerling GJ, Garbi N. Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen. Proc Natl Acad Sci U S A (2010) 107(13):5931-6. doi:10.1073/pnas.0911877107.
28. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med (1973) 137(5):1142-62. doi:10.1084/jem.137.5.1142.
29. Langerhans P. über die nerven der menschlichen haut. Virchows Arch (1868) 44(2):325-37. doi:10.1007/BF01959006.
30. Schuler G, Steinman RM. Murine epidermal langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med (1985) 161(3):526-46. doi:10.1084/jem.161.3.526.
31. Schuler G, Romani N, Steinman RM. A comparison of murine epidermal langerhans cells with spleen dendritic cells. J Invest Dermatol (1985) 85(1 Suppl):99s-106s. doi:10.1111/1523-1747.ep12275566.
32. Nussenzweig MC, Steinman RM. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med (1980) 151(5):1196-212. doi:10.1084/jem.151.5.1196.
33. Steinman RM, Witmer MD. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A (1978) 75(10):5132-6. doi:10.1073/pnas.75.10.5132.
34. Steinman RM, Gutchinov B, Witmer MD, Nussenzweig MC. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med (1983) 157(2):613-27. doi:10.1084/jem.157.2.613.
35. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D, Malosse C, et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity (2013) 39(5):925-38. doi:10.1016/j.immuni.2013.10.004.
36. Wilson NS, Villadangos JA. Lymphoid organ dendritic cells: beyond the langerhans cells paradigm. Immunol Cell Biol (2004) 82(1):91-8. doi:10.1111/j.1440-1711.2004.01216.x.
37. Romani N, Clausen BE, Stoitzner P. Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev (2010) 234(1):120-41. doi:10.1111/j.0105-2896.2009.00886.x.
38. Stoitzner P, Pfaller K, Stössel H, Romani N. A close-up view of migrating langerhans cells in the skin. J Invest Dermatol (2002) 118(1):117-25. doi:10.1046/j.0022-202x.2001.01631.x.
39. Takahara K, Omatsu Y, Yashima Y, Maeda Y, Tanaka S, Iyoda T, et al. Identification and expression of mouse langerin (CD207) in dendritic cells. Int Immunol (2002) 14(5):433-44. doi:10.1093/intimm/14.5.433.
40. Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, et al. Langerin, a novel c-type lectin specific to langerhans cells, is an endocytic receptor that induces the formation of birbeck granules. Immunity (2000) 12(1):71-81. doi:10.1016/S1074-7613(00)80160-0.
41. Valladeau J, Clair-Moninot V, Dezutter-Dambuyant C, Pin JJ, Kissenpfennig A, Mattéi MG, et al. Identification of mouse langerin/CD207 in langerhans cells and some dendritic cells of lymphoid tissues. J Immunol (2002) 168(2):782-92. doi:10.4049/jimmunol.168.2.782.
42. Cheong C, Idoyaga J, Do Y, Pack M, Park SH, Lee H, et al. Production of monoclonal antibodies that recognize the extracellular domain of mouse langerin/CD207. J Immunol Methods (2007) 324(1-2):48-62. doi:10.1016/j.jim.2007.05.001.
43. Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stössel H, Kapp M, et al. Visualization and characterization of migratory langerhans cells in murine skin and lymph nodes by antibodies against langerin/CD207. J Invest Dermatol (2003) 120(2):266-74. doi:10.1046/j.1523-1747.2003.12042.x.
44. Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML, et al. Inducible ablation of mouse langerhans cells diminishes but fails to abrogate contact hypersensitivity. J Cell Biol (2005) 169(4):569-76. doi:10.1083/jcb.200501071.
45. Kaplan DH, Jenison MC, Saeland S, Shlomchik WD, Shlomchik MJ. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity (2005) 23(6):611-20. doi:10.1016/j.immuni.2005.10.008.
46. Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, et al. Dynamics and function of langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating langerhans cells. Immunity (2005) 22(5):643-54. doi:10.1016/j.immuni.2005.04.004.
47. Bursch LS, Wang L, Igyarto B, Kissenpfennig A, Malissen B, Kaplan DH, et al. Identification of a novel population of langerin+ dendritic cells. J Exp Med (2007) 204(13):3147-56. doi:10.1084/jem.20071966.
48. Ginhoux F, Collin MP, Bogunovic M, Abel M, Leboeuf M, Helft J, et al. Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. J Exp Med (2007) 204(13):3133-46. doi:10.1084/jem.20071733.
49. Poulin LF, Henri S, de Bovis B, Devilard E, Kissenpfennig A, Malissen B. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal langerhans cells. J Exp Med (2007) 204(13):3119-31. doi:10.1084/jem.20071724.
50. Henri S, Guilliams M, Poulin LF, Tamoutounour S, Ardouin L, Dalod M, et al. Disentangling the complexity of the skin dendritic cell network. Immunol Cell Biol (2010) 88(4):366-75. doi:10.1038/icb.2010.34.
51. Henri S, Poulin LF, Tamoutounour S, Ardouin L, Guilliams M, de Bovis B, et al. CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of langerhans cells. J Exp Med (2010) 207(1):189-206. doi:10.1084/jem.20091964.
52. Bachem A, Hartung E, Güttler S, Mora A, Zhou X, Hegemann A, et al. Expression of XCR1 characterizes the batf3-dependent lineage of dendritic cells capable of antigen cross-presentation. Front Immunol (2012) 3:214. doi:10.3389/fimmu.2012.00214.
53. Crozat K, Tamoutounour S, Vu Manh TP, Fossum E, Luche H, Ardouin L, et al. Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the cd8a+ type. J Immunol (2011) 187(9):4411-5. doi:10.4049/jimmunol.1101717.
54. Merad M, Manz MG, Karsunky H, Wagers A, Peters W, Charo I, et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol (2002) 3(12):1135-41. doi:10.1038/ni852.
55. Kanitakis J, Morelon E, Petruzzo P, Badet L, Dubernard JM. Self-renewal capacity of human epidermal langerhans cells: observations made on a composite tissue allograft. Exp Dermatol (2011) 20(2):145-6. doi:10.1111/j.1600-0625.2010.01146.x.
56. Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M, Dai XM, et al. Langerhans cells arise from monocytes in vivo. Nat Immunol (2006) 7(3):265-73. doi:10.1038/ni1307.
57. Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T, Kitashima DY, et al. Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat Immunol (2012) 13(8):744-52. doi:10.1038/ni.2353.
58. Seré K, Baek JH, Ober-Blöbaum J, Müller-Newen G, Tacke F, Yokota Y, et al. Two distinct types of langerhans cells populate the skin during steady state and inflammation. Immunity (2012) 37(5):905-16. doi:10.1016/j.immuni.2012.07.019.
59. Sparber F, Scheffler JM, Amberg N, Tripp CH, Heib V, Hermann M, et al. The late endosomal adaptor molecule p14 (LAMTOR2) represents a novel regulator of langerhans cell homeostasis. Blood (2014) 123(2):217-27. doi:10.1182/blood-2013-08-518555.
60. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science (2010) 327(5966):656-61. doi:10.1126/science.1178331.
61. Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, et al. Adult langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med (2012) 209(6):1167-81. doi:10.1084/jem.20120340.
62. Chorro L, Sarde A, Li M, Woollard KJ, Chambon P, Malissen B, et al. Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med (2009) 206(13):3089-100. doi:10.1084/jem.20091586.
63. Tripp CH, Chang-Rodriguez S, Stoitzner P, Holzmann S, Stössel H, Douillard P, et al. Ontogeny of langerin/CD207 expression in the epidermis of mice. J Invest Dermatol (2004) 122(3):670-2. doi:10.1111/j.0022-202X.2004.22337.x.
64. Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M, Hashimoto D, et al. The origin and development of nonlymphoid tissue CD103+ dcs. J Exp Med (2009) 206(13):3115-30. doi:10.1084/jem.20091756.
65. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J, Leboeuf M, et al. Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity (2012) 37(6):1050-60. doi:10.1016/j.immuni.2012.11.001.
66. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of langerhans cells and microglia. Nat Immunol (2012) 13(8):753-60. doi:10.1038/ni.2360.
67. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol (2014) 14(8):571-8. doi:10.1038/nri3712.
68. Satpathy AT, Wu X, Albring JC, Murphy KM. Re(de)fining the dendritic cell lineage. Nat Immunol (2012) 13(12):1145-54. doi:10.1038/ni.2467.
69. Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell (2001) 106(3):255-8. doi:10.1016/S0092-8674(01)00449-4.
70. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med (1974) 139(2):380-97. doi:10.1084/jem.139.6.1431.
71. Witmer-Pack MD, Crowley MT, Inaba K, Steinman RM. Macrophages, but not dendritic cells, accumulate colloidal carbon following administration in situ. J Cell Sci (1993) 105(Pt 4):965-73.
72. Borkowski TA, Letterio JJ, Farr AG, Udey MC. A role for endogenous transforming growth factor beta 1 in langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal langerhans cells. J Exp Med (1996) 184(6):2417-22. doi:10.1084/jem.184.6.2417.
73. Kaplan DH, Li MO, Jenison MC, Shlomchik WD, Flavell RA, Shlomchik MJ. Autocrine/paracrine tgfbeta1 is required for the development of epidermal langerhans cells. J Exp Med (2007) 204(11):2545-52. doi:10.1084/jem.20071401.
74. Bobr A, Igyarto BZ, Haley KM, Li MO, Flavell RA, Kaplan DH. Autocrine/paracrine tgf-β1 inhibits langerhans cell migration. Proc Natl Acad Sci U S A (2012) 109(26):10492-7. doi:10.1073/pnas.1119178109.
75. Kel JM, Girard-Madoux MJ, Reizis B, Clausen BE. TGF-beta is required to maintain the pool of immature langerhans cells in the epidermis. J Immunol (2010) 185(6):3248-55. doi:10.4049/jimmunol.1000981.
76. Chopin M, Seillet C, Chevrier S, Wu L, Wang H, Morse HC, et al. Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks. J Exp Med (2013) 210(13):2967-80. doi:10.1084/jem.20130930.
77. Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D, et al. Runx3 regulates mouse tgf-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J (2004) 23(4):969-79. doi:10.1038/sj.emboj.7600085.
78. Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, Kuhl C, et al. Transcriptional profiling identifies id2 function in dendritic cell development. Nat Immunol (2003) 4(4):380-6. doi:10.1038/ni903.
79. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, Yao K, et al. In vivo analysis of dendritic cell development and homeostasis. Science (2009) 324(5925):392-7. doi:10.1126/science.1170540.
80. Maraskovsky E, Brasel K, Teepe M, Roux ER, Lyman SD, Shortman K, et al. Dramatic increase in the numbers of functionally mature dendritic cells in flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp Med (1996) 184(5):1953-62. doi:10.1084/jem.184.5.1953.
81. Waskow C, Liu K, Darrasse-Jèze G, Guermonprez P, Ginhoux F, Merad M, et al. The receptor tyrosine kinase flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol (2008) 9(6):676-83. doi:10.1038/ni.1615.
82. Mollah SA, Dobrin JS, Feder RE, Tse SW, Matos IG, Cheong C, et al. Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells. J Invest Dermatol (2014) 134(5):1265-75. doi:10.1038/jid.2013.515.
83. Vremec D, Lieschke GJ, Dunn AR, Robb L, Metcalf D, Shortman K. The influence of granulocyte/macrophage colony-stimulating factor on dendritic cell levels in mouse lymphoid organs. Eur J Immunol (1997) 27(1):40-4. doi:10.1002/eji.1830270107.
84. Greter M, Helft J, Chow A, Hashimoto D, Mortha A, Agudo-Cantero J, et al. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity (2012) 36(6):1031-46. doi:10.1016/j.immuni.2012.03.027.
85. Kingston D, Schmid MA, Onai N, Obata-Onai A, Baumjohann D, Manz MG. The concerted action of GM-CSF and flt3-ligand on in vivo dendritic cell homeostasis. Blood (2009) 114(4):835-43. doi:10.1182/blood-2009-02-206318.
86. Witmer-Pack MD, Hughes DA, Schuler G, Lawson L, McWilliam A, Inaba K, et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J Cell Sci (1993) 104(Pt 4):1021-9.
87. Ichikawa E, Hida S, Omatsu Y, Shimoyama S, Takahara K, Miyagawa S, et al. Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for IFN regulatory factor-2. Proc Natl Acad Sci U S A (2004) 101(11):3909-14. doi:10.1073/pnas.0400610101.
88. Akbari M, Honma K, Kimura D, Miyakoda M, Kimura K, Matsuyama T, et al. IRF4 in dendritic cells inhibits IL-12 production and controls th1 immune responses against leishmania major. J Immunol (2014) 192(5):2271-9. doi:10.4049/jimmunol.1301914.
89. Bajaña S, Roach K, Turner S, Paul J, Kovats S. IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation. J Immunol (2012) 189(7):3368-77. doi:10.4049/jimmunol.1102613.
90. Suzuki S, Honma K, Matsuyama T, Suzuki K, Toriyama K, Akitoyo I, et al. Critical roles of interferon regulatory factor 4 in cd11bhighcd8alpha-dendritic cell development. Proc Natl Acad Sci U S A (2004) 101(24):8981-6. doi:10.1073/pnas.0402139101.
91. Edelson BT, KC W, Juang R, Kohyama M, Benoit LA, Klekotka PA, et al. Peripheral CD103+ dendritic cells form a unified subset developmentally related to cd8alpha+ conventional dendritic cells. J Exp Med (2010) 207(4):823-36. doi:10.1084/jem.20091627.
92. Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, et al. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature (2015) 520(7545):104-8. doi:10.1038/nature14052.
93. Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H, O'Shea JJ, et al. IFN regulatory factor-4 and-8 govern dendritic cell subset development and their functional diversity. J Immunol (2005) 174(5):2573-81. doi:10.4049/jimmunol.174.5.2573.
94. Schiavoni G, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC, et al. ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of cd8alpha(+) dendritic cells. J Exp Med (2002) 196(11):1415-25. doi:10.1084/jem.20021263.
95. Mattei F, Schiavoni G, Borghi P, Venditti M, Canini I, Sestili P, et al. ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells. Blood (2006) 108(2):609-17. doi:10.1182/blood-2005-11-4490.
96. Schiavoni G, Mattei F, Borghi P, Sestili P, Venditti M, Morse HC, et al. ICSBP is critically involved in the normal development and trafficking of langerhans cells and dermal dendritic cells. Blood (2004) 103(6):2221-8. doi:10.1182/blood-2003-09-3007.
97. Orabona C, Puccetti P, Vacca C, Bicciato S, Luchini A, Fallarino F, et al. Toward the identification of a tolerogenic signature in ido-competent dendritic cells. Blood (2006) 107(7):2846-54. doi:10.1182/blood-2005-10-4077.
98. Edelson BT, Bradstreet TR, KC W, Hildner K, Herzog JW, Sim J, et al. Batf3-dependent cd11b(low/-) peripheral dendritic cells are gm-csf-independent and are not required for th cell priming after subcutaneous immunization. PLoS One (2011) 6(10):e25660. doi:10.1371/journal.pone.0025660.
99. Meredith MM, Liu K, Darrasse-Jeze G, Kamphorst AO, Schreiber HA, Guermonprez P, et al. Expression of the zinc finger transcription factor zdc (zbtb46, btbd4) defines the classical dendritic cell lineage. J Exp Med (2012) 209(6):1153-65. doi:10.1084/jem.20112675.
100. Satpathy AT, KC W, Albring JC, Edelson BT, Kretzer NM, Bhattacharya D, et al. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J Exp Med (2012) 209(6):1135-52. doi:10.1084/jem.20120030.
101. Sparber F, Tripp CH, Komenda K, Scheffler JM, Clausen BE, Huber LA, et al. The late endosomal adaptor molecule p14 (LAMTOR2) regulates tgfβ1-mediated homeostasis of langerhans cells. J Invest Dermatol (2014) 135(1):119-29. doi:10.1038/jid.2014.324.
102. Honda T, Egawa G, Grabbe S, Kabashima K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol (2013) 133(2):303-15. doi:10.1038/jid.2012.284.
103. Kaplan DH, Igyártó BZ, Gaspari AA. Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol (2012) 12(2):114-24. doi:10.1038/nri3150.
104. Bennett CL, Noordegraaf M, Martina CA, Clausen BE. Langerhans cells are required for efficient presentation of topically applied hapten to T cells. J Immunol (2007) 179(10):6830-5. doi:10.4049/jimmunol.179.10.6830.
105. Noordegraaf M, Flacher V, Stoitzner P, Clausen BE. Functional redundancy of langerhans cells and langerin+ dermal dendritic cells in contact hypersensitivity. J Invest Dermatol (2010) 130(12):2752-9. doi:10.1038/jid.2010.223.
106. Honda T, Nakajima S, Egawa G, Ogasawara K, Malissen B, Miyachi Y, et al. Compensatory role of langerhans cells and langerin-positive dermal dendritic cells in the sensitization phase of murine contact hypersensitivity. J Allergy Clin Immunol (2010) 125(5):1154.e-6.e. doi:10.1016/j.jaci.2009.12.005.
107. Bobr A, Olvera-Gomez I, Igyarto BZ, Haley KM, Hogquist KA, Kaplan DH. Acute ablation of langerhans cells enhances skin immune responses. J Immunol (2010) 185(8):4724-8. doi:10.4049/jimmunol.1001802.
108. Zahner SP, Kel JM, Martina CA, Brouwers-Haspels I, van Roon MA, Clausen BE. Conditional deletion of tgf-βr1 using langerin-cre mice results in langerhans cell deficiency and reduced contact hypersensitivity. J Immunol (2011) 187(10):5069-76. doi:10.4049/jimmunol.1101880.
109. Bacci S, Alard P, Dai R, Nakamura T, Streilein JW. High and low doses of haptens dictate whether dermal or epidermal antigen-presenting cells promote contact hypersensitivity. Eur J Immunol (1997) 27(2):442-8. doi:10.1002/eji.1830270214.
110. Clausen BE, Kel JM. Langerhans cells: critical regulators of skin immunity? Immunol Cell Biol (2010) 88(4):351-60. doi:10.1038/icb.2010.40.
111. Kaplan DH, Kissenpfennig A, Clausen BE. Insights into langerhans cell function from langerhans cell ablation models. Eur J Immunol (2008) 38(9):2369-76. doi:10.1002/eji.200838397.
112. Stoitzner P, Tripp CH, Douillard P, Saeland S, Romani N. Migratory langerhans cells in mouse lymph nodes in steady state and inflammation. J Invest Dermatol (2005) 125(1):116-25. doi:10.1111/j.0022-202X.2005.23757.x.
113. Bennett CL, Clausen BE. DC ablation in mice: promises, pitfalls, and challenges. Trends Immunol (2007) 28(12):525-31. doi:10.1016/j.it.2007.08.011.
114. Allan RS, Smith CM, Belz GT, van Lint AL, Wakim LM, Heath WR, et al. Epidermal viral immunity induced by cd8alpha+ dendritic cells but not by langerhans cells. Science (2003) 301(5641):1925-8. doi:10.1126/science.1087576.
115. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA, Zhan Y, et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity (2006) 25(1):153-62. doi:10.1016/j.immuni.2006.04.017.
116. Zhao X, Deak E, Soderberg K, Linehan M, Spezzano D, Zhu J, et al. Vaginal submucosal dendritic cells, but not langerhans cells, induce protective th1 responses to herpes simplex virus-2. J Exp Med (2003) 197(2):153-62. doi:10.1084/jem.20021109.
117. Bosnjak L, Miranda-Saksena M, Koelle DM, Boadle RA, Jones CA, Cunningham AL. Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells. J Immunol (2005) 174(4):2220-7. doi:10.4049/jimmunol.174.4.2220.
118. Jones CA, Fernandez M, Herc K, Bosnjak L, Miranda-Saksena M, Boadle RA, et al. Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro. J Virol (2003) 77(20):11139-49. doi:10.1128/JVI.77.20.11139-11149.2003.
119. Carbone FR, Belz GT, Heath WR. Transfer of antigen between migrating and lymph node-resident dcs in peripheral t-cell tolerance and immunity. Trends Immunol (2004) 25(12):655-8. doi:10.1016/j.it.2004.09.013.
120. He Y, Zhang J, Donahue C, Falo LD. Skin-derived dendritic cells induce potent CD8(+) T cell immunity in recombinant lentivector-mediated genetic immunization. Immunity (2006) 24(5):643-56. doi:10.1016/j.immuni.2006.03.014.
121. Bedoui S, Whitney PG, Waithman J, Eidsmo L, Wakim L, Caminschi I, et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat Immunol (2009) 10(5):488-95. doi:10.1038/ni.1724.
122. Bedoui S, Greyer M. The role of dendritic cells in immunity against primary herpes simplex virus infections. Front Microbiol (2014) 5:533. doi:10.3389/fmicb.2014.00533.
123. Moll H, Fuchs H, Blank C, RöllinghoffM. Langerhans cells transport leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells. Eur J Immunol (1993) 23(7):1595-601. doi:10.1002/eji.1830230730.
124. Ritter U, Meissner A, Scheidig C, Körner H. CD8 alpha-and langerin-negative dendritic cells, but not langerhans cells, act as principal antigen-presenting cells in leishmaniasis. Eur J Immunol (2004) 34(6):1542-50. doi:10.1002/eji.200324586.
125. Kautz-Neu K, Meyer RG, Clausen BE, von Stebut E. Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. Exp Dermatol (2010) 19(8):760-71. doi:10.1111/j.1600-0625.2010.01116.x.
126. Kautz-Neu K, Schwonberg K, Fischer MR, Schermann AI, von Stebut E. Dendritic cells in leishmania major infections: mechanisms of parasite uptake, cell activation and evidence for physiological relevance. Med Microbiol Immunol (2012) 201(4):581-92. doi:10.1007/s00430-012-0261-2.
127. Brewig N, Kissenpfennig A, Malissen B, Veit A, Bickert T, Fleischer B, et al. Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. J Immunol (2009) 182(2):774-83. doi:10.4049/jimmunol.182.2.774.
128. Reinhardt RL, Liang HE, Locksley RM. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol (2009) 10(4):385-93. doi:10.1038/ni.1715.
129. Zimara N, Florian C, Schmid M, Malissen B, Kissenpfennig A, Männel DN, et al. Langerhans cells promote early germinal center formation in response to leishmania-derived cutaneous antigens. Eur J Immunol (2014) 44(10):2955-67. doi:10.1002/eji.201344263.
130. Kautz-Neu K, Noordegraaf M, Dinges S, Bennett CL, John D, Clausen BE, et al. Langerhans cells are negative regulators of the anti-leishmania response. J Exp Med (2011) 208(5):885-91. doi:10.1084/jem.20102318.
131. Buch T, Heppner FL, Tertilt C, Heinen TJ, Kremer M, Wunderlich FT, et al. A cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods (2005) 2(6):419-26. doi:10.1038/nmeth762.
132. Belkaid Y, Hoffmann KF, Mendez S, Kamhawi S, Udey MC, Wynn TA, et al. The role of interleukin (IL)-10 in the persistence of leishmania major in the skin after healing and the therapeutic potential of anti-il-10 receptor antibody for sterile cure. J Exp Med (2001) 194(10):1497-506. doi:10.1084/jem.194.10.1497.
133. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control leishmania major persistence and immunity. Nature (2002) 420(6915):502-7. doi:10.1038/nature01152.
134. Gow NA, van de Veerdonk FL, Brown AJ, Netea MG. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol (2012) 10(2):112-22. doi:10.1038/nrmicro2711.
135. Lo HJ, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR, et al. Albicans mutants are avirulent. Cell (1997) 90(5):939-49. doi:10.1016/S0092-8674(00)80358-X.
136. Bär E, Whitney PG, Moor K, Reise Sousa C, LeibundGut-Landmann S. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity (2014) 40(1):117-27. doi:10.1016/j.immuni.2013.12.002.
137. Igyártó BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity (2011) 35(2):260-72. doi:10.1016/j.immuni.2011.06.005.
138. Kashem SW, Igyártó BZ, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, et al. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity (2015) 42(2):356-66. doi:10.1016/j.immuni.2015.01.008.
139. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, et al. Compartmentalized control of skin immunity by resident commensals. Science (2012) 337(6098):1115-9. doi:10.1126/science.1225152.
140. Seneschal J, Jiang X, Kupper TS. Langerin+ dermal DC, but not langerhans cells, are required for effective cd8-mediated immune responses after skin scarification with vaccinia virus. J Invest Dermatol (2014) 134(3):686-94. doi:10.1038/jid.2013.418.
141. Kim M, Truong NR, James V, Bosnjak L, Sandgren KJ, Harman AN, et al. Relay of herpes simplex virus between langerhans cells and dermal dendritic cells in human skin. PLoS Pathog (2015) 11(4):e1004812. doi:10.1371/journal.ppat.1004812.
142. Puttur FK, Fernandez MA, White R, Roediger B, Cunningham AL, Weninger W, et al. Herpes simplex virus infects skin gamma delta T cells before langerhans cells and impedes migration of infected langerhans cells by inducing apoptosis and blocking e-cadherin downregulation. J Immunol (2010) 185(1):477-87. doi:10.4049/jimmunol.0904106.
143. Azukizawa H, Kosaka H, Sano S, Heath WR, Takahashi I, Gao XH, et al. Induction of t-cell-mediated skin disease specific for antigen transgenically expressed in keratinocytes. Eur J Immunol (2003) 33(7):1879-88. doi:10.1002/eji.200323630.
144. Holcmann M, Stoitzner P, Drobits B, Luehrs P, Stingl G, Romani N, et al. Skin inflammation is not sufficient to break tolerance induced against a novel antigen. J Immunol (2009) 183(2):1133-43. doi:10.4049/jimmunol.0713351.
145. Shibaki A, Sato A, Vogel JC, Miyagawa F, Katz SI. Induction of gvhd-like skin disease by passively transferred CD8(+) t-cell receptor transgenic T cells into keratin 14-ovalbumin transgenic mice. J Invest Dermatol (2004) 123(1):109-15. doi:10.1111/j.0022-202X.2004.22701.x.
146. Bursch LS, Rich BE, Hogquist KA. Langerhans cells are not required for the CD8 T cell response to epidermal self-antigens. J Immunol (2009) 182(8):4657-64. doi:10.4049/jimmunol.0803656.
147. Kim BS, Miyagawa F, Cho YH, Bennett CL, Clausen BE, Katz SI. Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis. J Invest Dermatol (2009) 129(12):2805-17. doi:10.1038/jid.2009.176.
148. Stoitzner P, Tripp CH, Eberhart A, Price KM, Jung JY, Bursch L, et al. Langerhans cells cross-present antigen derived from skin. Proc Natl Acad Sci U S A (2006) 103(20):7783-8. doi:10.1073/pnas.0509307103.
149. Kurokawa I, Takahashi K, Moll I, Moll R. Expression of keratins in cutaneous epithelial tumors and related disorders-distribution and clinical significance. Exp Dermatol (2011) 20(3):217-28. doi:10.1111/j.1600-0625.2009.01006.x.
150. Grubauer G, Romani N, Kofler H, Stanzl U, Fritsch P, Hintner H. Apoptotic keratin bodies as autoantigen causing the production of igm-anti-keratin intermediate filament autoantibodies. J Invest Dermatol (1986) 87(4):466-71. doi:10.1111/1523-1747.ep12455510.
151. Holzmann S, Tripp CH, Schmuth M, Janke K, Koch F, Saeland S, et al. A model system using tape stripping for characterization of langerhans cell-precursors in vivo. J Invest Dermatol (2004) 122(5):1165-74. doi:10.1111/j.0022-202X.2004.22520.x.
152. Randolph GJ, Ochando J, Partida-Sánchez S. Migration of dendritic cell subsets and their precursors. Annu Rev Immunol (2008) 26:293-316. doi:10.1146/annurev.immunol.26.021607.090254.
153. Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, et al. Tumor immunotherapy by epicutaneous immunization requires langerhans cells. J Immunol (2008) 180(3):1991-8. doi:10.4049/jimmunol.180.3.1991.
154. Zaric M, Lyubomska O, Poux C, Hanna ML, McCrudden MT, Malissen B, et al. Dissolving microneedle delivery of nanoparticle-encapsulated antigen elicits efficient cross-priming and th1 immune responses by murine langerhans cells. J Invest Dermatol (2015) 135(2):425-34. doi:10.1038/jid.2014.415.
155. Flacher V, Tripp CH, Mairhofer DG, Steinman RM, Stoitzner P, Idoyaga J, et al. Murine langerin+ dermal dendritic cells prime CD8+ T cells while langerhans cells induce cross-tolerance. EMBO Mol Med (2014) 6(9):1191-204. doi:10.15252/emmm.201303283.
156. Karthaus N, Torensma R, Tel J. Deciphering the message broadcast by tumor-infiltrating dendritic cells. Am J Pathol (2012) 181(3):733-42. doi:10.1016/j.ajpath.2012.05.012.
157. Yanofsky VR, Mitsui H, Felsen D, Carucci JA. Understanding dendritic cells and their role in cutaneous carcinoma and cancer immunotherapy. Clin Dev Immunol (2013) 2013:624123. doi:10.1155/2013/624123.
158. Hargadon KM. Tumor-altered dendritic cell function: implications for anti-tumor immunity. Front Immunol (2013) 4:192. doi:10.3389/fimmu.2013.00192.
159. Bluth MJ, Zaba LC, Moussai D, Suárez-Fariñas M, Kaporis H, Fan L, et al. Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of t-cell proliferation. J Invest Dermatol (2009) 129(10):2451-62. doi:10.1038/jid.2009.96.
160. Nestle FO, Burg G, Fäh J, Wrone-Smith T, NickoloffBJ. Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells. Am J Pathol (1997) 150(2):641-51.
161. Fujita H, Suárez-Fariñas M, Mitsui H, Gonzalez J, Bluth MJ, Zhang S, et al. Langerhans cells from human cutaneous squamous cell carcinoma induce strong type 1 immunity. J Invest Dermatol (2012) 132(6):1645-55. doi:10.1038/jid.2012.34.
162. Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, et al. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science (2012) 335(6064):104-8. doi:10.1126/science.1211600.
163. Saeki M, Saito Y, Nagano M, Teshima R, Ozawa S, Sawada J. MRNA expression of multiple cytochrome p450 isozymes in four types of cultured skin cells. Int Arch Allergy Immunol (2002) 127(4):333-6. doi:10.1159/000057751.
164. Swanson HI. Cytochrome P450 expression in human keratinocytes: an aryl hydrocarbon receptor perspective. Chem Biol Interact (2004) 149(2-3):69-79. doi:10.1016/j.cbi.2004.08.006.
165. Lewis JM, Bürgler CD, Fraser JA, Liao H, Golubets K, Kucher CL, et al. Mechanisms of chemical cooperative carcinogenesis by epidermal langerhans cells. J Invest Dermatol (2015) 135(5):1405-14. doi:10.1038/jid.2014.411.
166. Clausen BE, Grabbe S. Multifaceted contributions of epidermal langerhans cells to cutaneous carcinogenesis. J Invest Dermatol (2015) 135(5):1218-20. doi:10.1038/jid.2014.520.
167. Lewis JM, Bürgler CD, Freudzon M, Golubets K, Gibson JF, Filler RB, et al. Langerhans cells facilitate uvb-induced epidermal carcinogenesis. J Invest Dermatol (2015). doi:10.1038/jid.2015.207.
168. Schwarz A, Noordegraaf M, Maeda A, Torii K, Clausen BE, Schwarz T. Langerhans cells are required for uvr-induced immunosuppression. J Invest Dermatol (2010) 130(5):1419-27. doi:10.1038/jid.2009.429.
169. Elentner A, Ortner D, Clausen BE, Gonzalez FJ, Fernández-Salguero PM, Schmuth M, et al. Skin response to a carcinogen involves the xenobiotic receptor pregnane X receptor. Exp Dermatol (2015). doi:10.1111/exd.12766.
170. Stene MA, Babajanians M, Bhuta S, Cochran AJ. Quantitative alterations in cutaneous langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol (1988) 91(2):125-8. doi:10.1111/1523-1747.ep12464142.
171. Toriyama K, Wen DR, Paul E, Cochran AJ. Variations in the distribution, frequency, and phenotype of langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol (1993) 100(3):269S-73S. doi:10.1111/1523-1747.ep12470135.
172. Ishida T, Oyama T, Carbone DP, Gabrilovich DI. Defective function of langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors. J Immunol (1998) 161(9):4842-51.
173. Movassagh M, Spatz A, Davoust J, Lebecque S, Romero P, Pittet M, et al. Selective accumulation of mature dc-lamp+ dendritic cells in tumor sites is associated with efficient t-cell-mediated antitumor response and control of metastatic dissemination in melanoma. Cancer Res (2004) 64(6):2192-8. doi:10.1158/0008-5472.CAN-03-2969.
174. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell (2014) 26(5):638-52. doi:10.1016/j.ccell.2014.09.007.
175. Broz ML, Krummel MF. The emerging understanding of myeloid cells as partners and targets in tumor rejection. Cancer Immunol Res (2015) 3(4):313-9. doi:10.1158/2326-6066.CIR-15-0041.
176. Starnes CO. Coley's toxins in perspective. Nature (1992) 357(6373):11-2. doi:10.1038/357011a0.
177. Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol (2012) 30:1-22. doi:10.1146/annurev-immunol-100311-102839.
178. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature (2007) 449(7161):419-26. doi:10.1038/nature06175.
179. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, et al. Vaccination of patients with b-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med (1996) 2(1):52-8. doi:10.1038/nm0196-52.
180. Sharma P, Allison JP. The future of immune checkpoint therapy. Science (2015) 348(6230):56-61. doi:10.1126/science.aaa8172.
181. Couzin-Frankel J. Breakthrough of the year 2013. Cancer Immunother Sci (2013) 342(6165):1432-3. doi:10.1126/science.342.6165.1432.
182. Delamarre L, Mellman I, Yadav M. Cancer immunotherapy. Neo approaches to cancer vaccines. Science (2015) 348(6236):760-1. doi:10.1126/science.aab3465.
183. Topalian SL, Wolchok JD, Chan TA, Mellman I, Palucka K, Banchereau J, et al. Immunotherapy: the path to win the war on cancer? Cell (2015) 161(2):185-6. doi:10.1016/j.cell.2015.03.045.
184. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science (2015) 348(6230):69-74. doi:10.1126/science.aaa4971.
185. Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity (2013) 39(1):38-48. doi:10.1016/j.immuni.2013.07.004.
186. Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, et al. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science (2015) 348(6236):803-8. doi:10.1126/science.aaa3828.
187. MartIn-Fontecha A, Sebastiani S, Höpken UE, Uguccioni M, Lipp M, Lanzavecchia A, et al. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med (2003) 198(4):615-21. doi:10.1084/jem.20030448.
188. Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature (2015) 519(7543):366-9. doi:10.1038/nature14320.
189. Tripp CH, Ebner S, Ratzinger G, Romani N, Stoitzner P. Conditioning of the injection site with cpg enhances the migration of adoptively transferred dendritic cells and endogenous CD8+ t-cell responses. J Immunother (2010) 33(2):115-25. doi:10.1097/CJI.0b013e3181b8ef5f.
190. Carmi Y, Spitzer MH, Linde IL, Burt BM, Prestwood TR, Perlman N, et al. Allogeneic igg combined with dendritic cell stimuli induce antitumour t-cell immunity. Nature (2015) 521(7550):99-104. doi:10.1038/nature14424.
191. Romano E, Cotari JW, Barreira da Silva R, Betts BC, Chung DJ, Avogadri F, et al. Human langerhans cells use an il-15r-a/IL-15/pstat5-dependent mechanism to break t-cell tolerance against the self-differentiation tumor antigen WT1. Blood (2012) 119(22):5182-90. doi:10.1182/blood-2011-09-382200.
192. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med (2001) 194(6):769-79. doi:10.1084/jem.194.6.769.
193. Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL, Nussenzweig M, et al. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class ii-positive lysosomal compartments. J Cell Biol (2000) 151(3):673-84. doi:10.1083/jcb.151.3.673.
194. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med (2004) 199(6):815-24. doi:10.1084/jem.20032220.
195. Romani N, Flacher V, Tripp CH, Sparber F, Ebner S, Stoitzner P. Targeting skin dendritic cells to improve intradermal vaccination. Curr Top Microbiol Immunol (2012) 351:113-38. doi:10.1007/82_2010_118.
196. Tacken PJ, de Vries IJ, Torensma R, Figdor CG. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol (2007) 7(10):790-802. doi:10.1038/nri2173.
197. Carter RW, Thompson C, Reid DM, Wong SY, Tough DF. Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated c-type lectin-1. J Immunol (2006) 177(4):2276-84. doi:10.4049/jimmunol.177.4.2276.
198. Flacher V, Tripp CH, Haid B, Kissenpfennig A, Malissen B, Stoitzner P, et al. Skin langerin+ dendritic cells transport intradermally injected anti-dec-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses. J Immunol (2012) 188(5):2146-55. doi:10.4049/jimmunol.1004120.
199. Idoyaga J, Cheong C, Suda K, Suda N, Kim JY, Lee H, et al. Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J Immunol (2008) 180(6):3647-50. doi:10.4049/jimmunol.180.6.3647.
200. Johnson TS, Mahnke K, Storn V, Schönfeld K, Ring S, Nettelbeck DM, et al. Inhibition of melanoma growth by targeting of antigen to dendritic cells via an anti-dec-205 single-chain fragment variable molecule. Clin Cancer Res (2008) 14(24):8169-77. doi:10.1158/1078-0432.CCR-08-1474.
201. Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH. Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res (2005) 65(15):7007-12. doi:10.1158/0008-5472.CAN-05-0938.
202. Hartung E, Becker M, Bachem A, Reeg N, Jäkel A, HutloffA, et al. Induction of potent CD8 T cell cytotoxicity by specific targeting of antigen to cross-presenting dendritic cells in vivo via murine or human XCR1. J Immunol (2015) 194(3):1069-79. doi:10.4049/jimmunol.1401903.
203. Terhorst D, Fossum E, Baranska A, Tamoutounour S, Malosse C, Garbani M, et al. Laser-Assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses. J Immunol (2015) 194(12):5895-902. doi:10.4049/jimmunol.1500564.
204. Dhodapkar MV, Sznol M, Zhao B, Wang D, Carvajal RD, Keohan ML, et al. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med (2014) 6(232):232ra51. doi:10.1126/scitranslmed.3008068.
205. Engelke L, Winter G, Hook S, Engert J. Recent insights into cutaneous immunization: how to vaccinate via the skin. Vaccine (2015) 33(37):4663-74. doi:10.1016/j.vaccine.2015.05.012.
206. Stoitzner P, Sparber F, Tripp CH. Langerhans cells as targets for immunotherapy against skin cancer. Immunol Cell Biol (2010) 88(4):431-7. doi:10.1038/icb.2010.31.
207. Rechtsteiner G, Warger T, Osterloh P, Schild H, Radsak MP. Cutting edge: priming of CTL by transcutaneous peptide immunization with imiquimod. J Immunol (2005) 174(5):2476-80. doi:10.4049/jimmunol.174.5.2476.
208. Seo N, Tokura Y, Nishijima T, Hashizume H, Furukawa F, Takigawa M. Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis. Proc Natl Acad Sci U S A (2000) 97(1):371-6. doi:10.1073/pnas.97.1.371.
209. Frech SA, Dupont HL, Bourgeois AL, McKenzie R, Belkind-Gerson J, Figueroa JF, et al. Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial. Lancet (2008) 371(9629):2019-25. doi:10.1016/S0140-6736(08)60839-9.
210. Yagi H, Hashizume H, Horibe T, Yoshinari Y, Hata M, Ohshima A, et al. Induction of therapeutically relevant cytotoxic T lymphocytes in humans by percutaneous peptide immunization. Cancer Res (2006) 66(20):10136-44. doi:10.1158/0008-5472.CAN-06-1029.
211. Sullivan SP, Koutsonanos DG, Del Pilar Martin M, Lee JW, Zarnitsyn V, Choi SO, et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med (2010) 16(8):915-20. doi:10.1038/nm.2182.
212. Crozat K, Guiton R, Guilliams M, Henri S, Baranek T, Schwartz-Cornil I, et al. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol Rev (2010) 234(1):177-98. doi:10.1111/j.0105-2896.2009.00868.x.
213. Guilliams M, Henri S, Tamoutounour S, Ardouin L, Schwartz-Cornil I, Dalod M, et al. From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets. Eur J Immunol (2010) 40(8):2089-94. doi:10.1002/eji.201040498.
214. Haniffa M, Shin A, Bigley V, McGovern N, Teo P, See P, et al. Human tissues contain cd141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity (2012) 37(1):60-73. doi:10.1016/j.immuni.2012.04.012.
215. Haniffa M, Gunawan M, Jardine L. Human skin dendritic cells in health and disease. J Dermatol Sci (2015) 77(2):85-92. doi:10.1016/j.jdermsci.2014.08.012.
216. McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A, Poyner E, et al. Human dermal CD14+ cells are a transient population of monocyte-derived macrophages. Immunity (2014) 41(3):465-77. doi:10.1016/j.immuni.2014.08.006.
217. Zaba LC, Fuentes-Duculan J, Steinman RM, Krueger JG, Lowes MA. Normal human dermis contains distinct populations of cd11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages. J Clin Invest (2007) 117(9):2517-25. doi:10.1172/JCI32282.
218. Chu CC, Ali N, Karagiannis P, Di Meglio P, Skowera A, Napolitano L, et al. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J Exp Med (2012) 209(5):935-45. doi:10.1084/jem.20112583.
219. Bigley V, McGovern N, Milne P, Dickinson R, Pagan S, Cookson S, et al. Langerin-expressing dendritic cells in human tissues are related to cd1c+ dendritic cells and distinct from langerhans cells and cd141high XCR1+ dendritic cells. J Leukoc Biol (2015) 97(4):627-34. doi:10.1189/jlb.1HI0714-351R.
220. Klechevsky E, Morita R, Liu M, Cao Y, Coquery S, Thompson-Snipes L, et al. Functional specializations of human epidermal langerhans cells and CD14+ dermal dendritic cells. Immunity (2008) 29(3):497-510. doi:10.1016/j.immuni.2008.07.013.
221. Ebner S, Nguyen VA, Forstner M, Wang YH, Wolfram D, Liu YJ, et al. Thymic stromal lymphopoietin converts human epidermal langerhans cells into antigen-presenting cells that induce proallergic T cells. J Allergy Clin Immunol (2007) 119(4):982-90. doi:10.1016/j.jaci.2007.01.003.
222. Artyomov MN, Munk A, Gorvel L, Korenfeld D, Cella M, Tung T, et al. Modular expression analysis reveals functional conservation between human langerhans cells and mouse cross-priming dendritic cells. J Exp Med (2015) 212(5):743-57. doi:10.1084/jem.20131675.
223. Stoitzner P, Schaffenrath S, Tripp CH, Reider D, Komenda K, Del Frari B, et al. Human skin dendritic cells can be targeted in situ by intradermal injection of antibodies against lectin receptors. Exp Dermatol (2014) 23(12):909-15. doi:10.1111/exd.12573.
224. Hänsel A, Günther C, Ingwersen J, Starke J, Schmitz M, Bachmann M, et al. Human slan (6-sulfo lacnac) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 t-cell responses. J Allergy Clin Immunol (2011) 127(3):787-94.e1-9. doi:10.1016/j.jaci.2010.12.009.
225. Zaba LC, Krueger JG, Lowes MA. Resident and "inflammatory" dendritic cells in human skin. J Invest Dermatol (2009) 129(2):302-8. doi:10.1038/jid.2008.225.
226. Banchereau J, Thompson-Snipes L, Zurawski S, Blanck JP, Cao Y, Clayton S, et al. The differential production of cytokines by human langerhans cells and dermal CD14(+) dcs controls CTL priming. Blood (2012) 119(24):5742-9. doi:10.1182/blood-2011-08-371245.
227. Ratzinger G, Baggers J, de Cos MA, Yuan J, Dao T, Reagan JL, et al. Mature human langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive il-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells. J Immunol (2004) 173(4):2780-91. doi:10.4049/jimmunol.173.4.2780.
228. Denoeud J, Moser M. Role of CD27/CD70 pathway of activation in immunity and tolerance. J Leukoc Biol (2011) 89(2):195-203. doi:10.1189/jlb.0610351.
229. Polak ME, Newell L, Taraban VY, Pickard C, Healy E, Friedmann PS, et al. CD70-CD27 interaction augments CD8+ t-cell activation by human epidermal langerhans cells. J Invest Dermatol (2012) 132(6):1636-44. doi:10.1038/jid.2012.26.
230. van der Aar AM, de Groot R, Sanchez-Hernandez M, Taanman EW, van Lier RA, Teunissen MB, et al. Cutting edge: virus selectively primes human langerhans cells for CD70 expression promoting CD8+ T cell responses. J Immunol (2011) 187(7):3488-92. doi:10.4049/jimmunol.1101105.
231. Jelinek I, Leonard JN, Price GE, Brown KN, Meyer-Manlapat A, Goldsmith PK, et al. TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J Immunol (2011) 186(4):2422-9. doi:10.4049/jimmunol.1002845.
232. Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A (2002) 99(1):351-8. doi:10.1073/pnas.231606698.
233. Pulendran B, Tang H, Denning TL. Division of labor, plasticity, and crosstalk between dendritic cell subsets. Curr Opin Immunol (2008) 20(1):61-7. doi:10.1016/j.coi.2007.10.009.
234. Romani N, Brunner PM, Stingl G. Changing views of the role of langerhans cells. J Invest Dermatol (2012) 132(3 Pt 2):872-81. doi:10.1038/jid.2011.437.