Autoinflammatory Skin Disorders: The Inflammasomme in Focus

Trends in Molecular Medicine

Volumn 22, Issue 7, 2016, Pages 545-564

  Gurung, Prajwal ^a   Kanneganti, Thirumala Devi ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

autoimmune; CAPS; FMF; IL 1; inflammasome; inflammatory; NLRP3; Ptpn6; Sharpin

Indexed keywords

CANAKINUMAB; CASPASE 8; CATHEPSIN; CHYMASE; CHYMOTRYPSIN; COLCHICINE; CRYOPYRIN; ELASTASE; GASDERMIN D; GELATINASE B; GRANZYME A; IMMUNOGLOBULIN E; INFLAMMASOME; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 17; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 4; MYELOBLASTIN; MYELOID DIFFERENTIATION FACTOR 88; PROLINE SERINE THREONINE PHOSPHATASE INTERACTING PROTEIN 1; PROTEIN; PROTEIN TYROSINE PHOSPHATASE SHP 1; PYRIN DOMAIN ONLY PROTEIN 1; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RILONACEPT; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG; INTERLEUKIN 1;

ACUTE FEBRILE NEUTROPHILIC DERMATOSIS; ADAPTIVE IMMUNITY; APOPTOSIS; AUTOINFLAMMATORY DISEASE; AUTOSOMAL DOMINANT INHERITANCE; BASOPHIL; BONE MARROW DERIVED MACROPHAGE; CD4+ T LYMPHOCYTE; CELL DEATH; CELL INFILTRATION; CELL MATURATION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CHROMOSOME 16; CINCA SYNDROME; CYTOKINE PRODUCTION; DENDRITIC CELL; DERMATITIS; DERMIS; EPIDERMIS; EXON; FAMILIAL MEDITERRANEAN FEVER; HAIR LOSS; HELPER CELL; HEPATOMEGALY; HEPATOSPLENOMEGALY; HUMAN; IMMUNOCOMPETENT CELL; KERATINOCYTE; LEUKOCYTOSIS; LYMPHADENOPATHY; MACROPHAGE; MAST CELL; MISSENSE MUTATION; MONOCYTE; MUCKLE WELLS SYNDROME; NECROPTOSIS; NEUTROPHIL; NONHUMAN; PAPA SYNDROME; POTASSIUM TRANSPORT; PYODERMA GANGRENOSUM; PYROPTOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SIGNAL TRANSDUCTION; SKIN ABSCESS; SKIN CELL; SPLENOMEGALY; SPONTANEOUS MUTATION; SUBCORNEAL PUSTULAR DERMATOSIS; ANIMAL; DISEASE MODEL; IMMUNOLOGY; PATHOLOGY; SKIN;

ANIMALS; CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES; DISEASE MODELS, ANIMAL; FAMILIAL MEDITERRANEAN FEVER; HUMANS; INFLAMMASOMES; INTERLEUKIN-1; SKIN;

EID: 84971597411     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2016.05.003     Document Type: Review

References (141)

1. 1 Pasparakis, M., et al. Mechanisms regulating skin immunity and inflammation. Nat. Rev. Immunol. 14 (2014), 289–301.
2. 2 Grice, E.A., et al. Topographical and temporal diversity of the human skin microbiome. Science 324 (2009), 1190–1192.
3. 3 Gallo, R.L., Nakatsuji, T., Microbial symbiosis with the innate immune defense system of the skin. J. Invest. Dermatol. 131 (2011), 1974–1980.
4. 4 Iwase, T., et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465 (2010), 346–349.
5. 5 Naik, S., et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520 (2015), 104–108.
6. 6 Naik, S., et al. Compartmentalized control of skin immunity by resident commensals. Science 337 (2012), 1115–1119.
7. 7 Sanford, J.A., Gallo, R.L., Functions of the skin microbiota in health and disease. Semin. Immunol. 25 (2013), 370–377.
8. 8 Nestle, F.O., et al. Skin immune sentinels in health and disease. Nat. Rev. Immunol. 9 (2009), 679–691.
9. 9 Goldbach-Mansky, R., Blocking interleukin-1 in rheumatic diseases. Ann. N.Y. Acad. Sci. 1182 (2009), 111–123.
10. 10 Dinarello, C.A., Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117 (2011), 3720–3732.
11. 11 Lukens, J.R., Kanneganti, T.D., Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease. Semin. Immunopathol. 36 (2014), 595–609.
12. 12 Man, S.M., Kanneganti, T.D., Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol. 16 (2016), 7–21.
13. 13 Gurung, P., et al. Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol. Med. 21 (2015), 193–201.
14. 14 Kayagaki, N., et al. Non-canonical inflammasome activation targets caspase-11. Nature 479 (2011), 117–121.
15. 15 Fettelschoss, A., et al. Inflammasome activation and IL-1beta target IL-1alpha for secretion as opposed to surface expression. Proc. Natl. Acad. Sci. U.S.A. 108 (2011), 18055–18060.
16. 16 Shi, J., et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526 (2015), 660–665.
17. 17 Kayagaki, N., et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526 (2015), 666–671.
18. 18 Gurung, P., Kanneganti, T.D., Novel roles for caspase-8 in IL-1beta and inflammasome regulation. Am. J. Pathol. 185 (2015), 17–25.
19. 19 Kuemmerle-Deschner, J.B., CAPS – pathogenesis, presentation and treatment of an autoinflammatory disease. Semin. Immunopathol. 37 (2015), 377–385.
20. 20 Prieur, A.M., et al. A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J. Rheumatol. Suppl. 66 (1987), 57–68.
21. 21 Hoffman, H.M., et al. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J. Allergy Clin. Immunol. 108 (2001), 615–620.
22. 22 Hoffman, H.M., et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome. Nat. Genet. 29 (2001), 301–305.
23. 23 Feldmann, J., et al. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am. J. Hum. Genet. 71 (2002), 198–203.
24. 24 Aksentijevich, I., et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum. 46 (2002), 3340–3348.
25. 25 Milhavet, F., et al. The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum. Mutat. 29 (2008), 803–808.
26. 26 Hoffman, H.M., et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 364 (2004), 1779–1785.
27. 27 Hawkins, P.N., et al. Interleukin-1-receptor antagonist in the Muckle–Wells syndrome. N. Engl. J. Med. 348 (2003), 2583–2584.
28. 28 Hawkins, P.N., et al. Spectrum of clinical features in Muckle–Wells syndrome and response to anakinra. Arthritis Rheum. 50 (2004), 607–612.
29. 29 Goldbach-Mansky, R., et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N. Engl. J. Med. 355 (2006), 581–592.
30. 30 Goldbach-Mansky, R., et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 58 (2008), 2432–2442.
31. 31 Hoffman, H.M., et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 58 (2008), 2443–2452.
32. 32 Lachmann, H.J., et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360 (2009), 2416–2425.
33. 33 Dhimolea, E., Canakinumab. MAbs 2 (2010), 3–13.
34. 34 Alten, R., et al. The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis. Arthritis Res. Ther., 10, 2008, R67.
35. 35 Martinon, F., et al. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10 (2002), 417–426.
36. 36 Agostini, L., et al. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle–Wells autoinflammatory disorder. Immunity 20 (2004), 319–325.
37. 37 Martinon, F., et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440 (2006), 237–241.
38. 38 Mariathasan, S., et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440 (2006), 228–232.
39. 39 Kanneganti, T.D., et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440 (2006), 233–236.
40. 40 Meng, G., et al. A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30 (2009), 860–874.
41. 41 Brydges, S.D., et al. Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity. Immunity 30 (2009), 875–887.
42. 42 Gurung, P., et al. Chronic TLR stimulation controls NLRP3 inflammasome activation through IL-10 mediated regulation of NLRP3 expression and caspase-8 activation. Sci. Rep., 5, 2015, 14488.
43. + efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38 (2013), 1142–1153.
44. 44 Perregaux, D., Gabel, C.A., Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. J. Biol. Chem. 269 (1994), 15195–15203.
45. 45 Petrilli, V., et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14 (2007), 1583–1589.
46. 46 Juliana, C., et al. Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J. Biol. Chem. 287 (2012), 36617–36622.
47. 47 Py, B.F., et al. Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Mol. Cell 49 (2013), 331–338.
48. 48 Spalinger, M.R., et al. NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22. J. Clin. Invest. 126 (2016), 1783–1800.
49. 49 de Almeida, L., et al. The PYRIN domain-only protein POP1 inhibits inflammasome assembly and ameliorates inflammatory disease. Immunity 43 (2015), 264–276.
50. 50 Nakamura, Y., et al. Critical role for mast cells in interleukin-1beta-driven skin inflammation associated with an activating mutation in the Nlrp3 protein. Immunity 37 (2012), 85–95.
51. 51 Centola, M., et al. The hereditary periodic fever syndromes: molecular analysis of a new family of inflammatory diseases. Hum. Mol. Genet. 7 (1998), 1581–1588.
52. 52 Brydges, S., Kastner, D.L., The systemic autoinflammatory diseases: inborn errors of the innate immune system. Curr. Top Microbiol. Immunol. 305 (2006), 127–160.
53. 53 Azizi, E., Fisher, B.K., Cutaneous manifestations of familial Mediterranean fever. Arch. Dermatol. 112 (1976), 364–366.
54. 54 French, F.M.F.C., A candidate gene for familial Mediterranean fever. Nat. Genet. 17 (1997), 25–31.
55. 55 The International FMF Consortium, Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90 (1997), 797–807.
56. 56 Marek-Yagel, D., et al. Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis Rheum. 60 (2009), 1862–1866.
57. 57 Booty, M.G., et al. Familial Mediterranean fever with a single MEFV mutation: where is the second hit?. Arthritis Rheum. 60 (2009), 1851–1861.
58. 58 Chae, J.J., et al. Isolation, genomic organization, and expression analysis of the mouse and rat homologs of MEFV, the gene for familial Mediterranean fever. Mamm. Genome 11 (2000), 428–435.
59. 59 Masters, S.L., et al. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci. Transl. Med., 8, 2016, 332ra345.
60. 60 Wang, D., et al. Inflammation in mice ectopically expressing human pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome-associated PSTPIP1 A230T mutant proteins. J. Biol. Chem. 288 (2013), 4594–4601.
61. 61 Wise, C.A., et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum. Mol. Genet. 11 (2002), 961–969.
62. 62 Shoham, N.G., et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc. Natl. Acad. Sci. U.S.A. 100 (2003), 13501–13506.
63. 63 Dinarello, C.A., et al. Colchicine therapy for familial Mediterranean fever. A double-blind trial. N. Engl. J. Med. 291 (1974), 934–937.
64. 64 Ozkaya, N., Yalcinkaya, F., Colchicine treatment in children with familial Mediterranean fever. Clin. Rheumatol. 22 (2003), 314–317.
65. 65 Manukyan, G., Aminov, R., Update on pyrin functions and mechanisms of familial Mediterranean fever. Front. Microbiol., 7, 2016, 456.
66. 66 Zemer, D., et al. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N. Engl. J. Med. 314 (1986), 1001–1005.
67. 67 Bilgen, S.A., et al. Effects of anti-tumor necrosis factor agents for familial Mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment. J. Clin. Rheumatol. 17 (2011), 358–362.
68. 68 Ozgocmen, S., Akgul, O., Anti-TNF agents in familial Mediterranean fever: report of three cases and review of the literature. Mod. Rheumatol. 21 (2011), 684–690.
69. 69 Ozcakar, Z.B., et al. Infliximab therapy for familial Mediterranean fever-related amyloidosis: case series with long term follow-up. Clin. Rheumatol. 31 (2012), 1267–1271.
70. 70 Ozcakar, Z.B., et al. Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis. Clin. Rheumatol. 35 (2016), 441–446.
71. 71 Chae, J.J., et al. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol. Cell 11 (2003), 591–604.
72. 72 Xu, H., et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature 513 (2014), 237–241.
73. 73 Gavrilin, M.A., et al. Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia. J. Immunol. 188 (2012), 3469–3477.
74. 74 Touitou, I., The spectrum of familial Mediterranean fever (FMF) mutations. Eur. J. Hum. Genet. 9 (2001), 473–483.
75. 75 Chae, J.J., et al. Gain-of-function pyrin mutations induce NLRP3 protein-independent interleukin-1beta activation and severe autoinflammation in mice. Immunity 34 (2011), 755–768.
76. 76 Kim, M.L., et al. Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1beta. J. Exp. Med. 212 (2015), 927–938.
77. 77 HogenEsch, H., et al. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. Am. J. Pathol. 143 (1993), 972–982.
78. 78 Seymour, R.E., et al. Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis. Genes Immun. 8 (2007), 416–421.
79. 79 Tokunaga, F., et al. SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. Nature 471 (2011), 633–636.
80. 80 Ikeda, F., et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature 471 (2011), 637–641.
81. 81 Gerlach, B., et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471 (2011), 591–596.
82. 82 Kirisako, T., et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25 (2006), 4877–4887.
83. 83 Gurung, P., et al. Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation. J. Immunol. 194 (2015), 2064–2067.
84. 84 Rodgers, M.A., et al. The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation. J. Exp. Med. 211 (2014), 1333–1347.
85. 85 Liang, Y., et al. Inhibition of NF-kappaB signaling retards eosinophilic dermatitis in SHARPIN-deficient mice. J. Invest. Dermatol. 131 (2011), 141–149.
86. 86 Rickard, J.A., et al. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. Elife, 3, 2014, e03464.
87. 87 Douglas, T., et al. The inflammatory caspases-1 and -11 mediate the pathogenesis of dermatitis in Sharpin-deficient mice. J. Immunol. 195 (2015), 2365–2373.
88. 88 Gijbels, M.J., et al. Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa. J. Invest. Dermatol. 105 (1995), 769–773.
89. 89 Kumari, S., et al. Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. Elife, 3, 2014, e03422.
90. 90 Berger, S.B., et al. Cutting edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J. Immunol. 192 (2014), 5476–5480.
91. 91 Iyer, S.S., et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. U.S.A. 106 (2009), 20388–20393.
92. 92 Nesterovitch, A.B., et al. Spontaneous insertion of a b2 element in the Ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans. Am. J. Pathol. 178 (2011), 1701–1714.
93. 93 Lukens, J.R., et al. RIP1-driven autoinflammation targets IL-1alpha independently of inflammasomes and RIP3. Nature 498 (2013), 224–227.
94. 94 Nesterovitch, A.B., et al. Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses. Am. J. Pathol. 178 (2011), 1434–1441.
95. 95 Pao, L.I., et al. Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annu. Rev. Immunol. 25 (2007), 473–523.
96. 96 Tibaldi, E., et al. Lyn-mediated SHP-1 recruitment to CD5 contributes to resistance to apoptosis of B-cell chronic lymphocytic leukemia cells. Leukemia 25 (2011), 1768–1781.
97. 97 Eriksen, K.W., et al. Deficient SOCS3 and SHP-1 expression in psoriatic T cells. J. Invest. Dermatol. 130 (2010), 1590–1597.
98. 98 Christophi, G.P., et al. SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients. Lab. Invest. 88 (2008), 243–255.
99. 99 Cao, H., Hegele, R.A., Identification of polymorphisms in the human SHP1 gene. J. Hum. Genet. 47 (2002), 445–447.
100. 100 Tsui, H.W., et al. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat. Genet. 4 (1993), 124–129.
101. 101 Shultz, L.D., et al. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73 (1993), 1445–1454.
102. 102 Shultz, L.D., et al. ‘Viable motheaten,’ a new allele at the motheaten locus. I. Pathology. Am. J. Pathol. 116 (1984), 179–192.
103. 103 Green, M.C., Shultz, L.D., Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J. Hered. 66 (1975), 250–258.
104. 104 Croker, B.A., et al. Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. Proc. Natl. Acad. Sci. U.S.A. 105 (2008), 15028–15033.
105. 105 Groves, R.W., et al. Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis. Proc. Natl. Acad. Sci. U.S.A. 92 (1995), 11874–11878.
106. 106 Luheshi, N.M., et al. Dual functionality of interleukin-1 family cytokines: implications for anti-interleukin-1 therapy. Br. J. Pharmacol. 157 (2009), 1318–1329.
107. 107 Cohen, I., et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl. Acad. Sci. U.S.A. 107 (2010), 2574–2579.
108. 108 Chen, C.J., et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat. Med. 13 (2007), 851–856.
109. 109 Kelliher, M.A., et al. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 8 (1998), 297–303.
110. 110 Gurung, P., et al. NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1beta-mediated osteomyelitis. Proc. Natl. Acad. Sci. U.S.A. 113 (2016), 4452–4457.
111. 111 Lukens, J.R., et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 516 (2014), 246–249.
112. 112 Romani, N., et al. Epidermal Langerhans cells – changing views on their function in vivo. Immunol. Lett. 106 (2006), 119–125.
113. 113 Hoeffel, G., et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209 (2012), 1167–1181.
114. + dermal dendritic cells. Immunity 29 (2008), 497–510.
115. 115 Bennett, C.L., et al. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J. Cell Biol. 169 (2005), 569–576.
116. 116 Kissenpfennig, A., et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22 (2005), 643–654.
117. 117 Saito, M., et al. Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat. Biotechnol. 19 (2001), 746–750.
118. 118 Seneschal, J., et al. Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 36 (2012), 873–884.
119. + T cells are resident in normal skin. J. Immunol. 176 (2006), 4431–4439.
120. 120 Heath, W.R., Carbone, F.R., The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat. Immunol. 14 (2013), 978–985.
121. RM cells providing global skin immunity. Nature 483 (2012), 227–231.
122. + T cells. Nat. Immunol. 14 (2013), 509–513.
123. 123 Havran, W.L., et al. Recognition of self antigens by skin-derived T cells with invariant gamma delta antigen receptors. Science 252 (1991), 1430–1432.
124. 124 Toulon, A., et al. A role for human skin-resident T cells in wound healing. J. Exp. Med. 206 (2009), 743–750.
125. 125 Tamoutounour, S., et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39 (2013), 925–938.
126. 126 Gunther, C., et al. Human 6-sulfo LacNAc (slan) dendritic cells are a major population of dermal dendritic cells in steady state and inflammation. Clin. Exp. Dermatol. 37 (2012), 169–176.
127. 127 Nestle, F.O., et al. Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. J. Immunol. 151 (1993), 6535–6545.
128. 128 Igyarto, B.Z., et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35 (2011), 260–272.
129. + dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39 (2013), 733–743.
130. 130 Gao, Y., et al. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39 (2013), 722–732.
131. neg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proc. Natl. Acad. Sci. U.S.A. 110 (2013), 10723–10728.
132. 132 Jenkins, S.J., et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332 (2011), 1284–1288.
133. 133 Jakubzick, C., et al. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39 (2013), 599–610.
134. + T cells with a distinct phenotype and migratory pattern. J. Immunol. 190 (2013), 970–976.
135. + skin-resident T cells in human herpes virus infection. Nature 497 (2013), 494–497.
136. + T cells. Nature 477 (2011), 216–219.
137. 137 Gebhardt, T., et al. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 10 (2009), 524–530.
138. 138 Wernersson, S., Pejler, G., Mast cell secretory granules: armed for battle. Nat. Rev. Immunol. 14 (2014), 478–494.
139. 139 St John, A.L., et al. Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance. Proc. Natl. Acad. Sci. U.S.A. 108 (2011), 9190–9195.
140. 140 Nakamura, Y., et al. Staphylococcus delta-toxin induces allergic skin disease by activating mast cells. Nature 503 (2013), 397–401.
141. 141 Wang, H., et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell 54 (2014), 133–146.