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Inflammasome in the Skin

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The Inflammasomes

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

The skin, our largest organ, protects us from our environment and is therefore constantly subjected to microbial, chemical, and physical insults. Not surprisingly, it is endowed with the capacity to detect these events and respond accordingly, alerting the immune system when needed, often through the inflammasome. In this chapter, we propose a synthetic view of the role and implication of the inflammasome in the skin. We will consider first the molecular events leading to its activation and the consequences of IL-1β secretion, and then lessons from the bedside, reviewing diseases that are inflammasome dependent and their effect on the skin.

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References

  1. Kupper TS, Fuhlbrigge RC (2004) Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 4:211–222

    Article  PubMed  CAS  Google Scholar 

  2. Murphy JE, Robert C, Kupper TS (2000) Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity. J Invest Dermatol 114:602–608

    Article  PubMed  CAS  Google Scholar 

  3. Martinon F, Tschopp J (2005) NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26:447–454

    Article  PubMed  CAS  Google Scholar 

  4. Watanabe H, Gaide O, Petrilli V, Martinon F, Contassot E, Roques S, Kummer JA, Tschopp J, French LE (2007) Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol 127:1956–1963

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan DH, Kissenpfennig A, Clausen BE (2008) Insights into Langerhans cell function from Langerhans cell ablation models. Eur J Immunol 38:2369–2376

    Article  PubMed  CAS  Google Scholar 

  6. Baker BS, Ovigne JM, Powles AV, Corcoran S, Fry L (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148:670–679

    Article  PubMed  CAS  Google Scholar 

  7. Miller LS (2008) Toll-like receptors in skin. Adv Dermatol 24:71–87

    Article  PubMed  Google Scholar 

  8. Lenz A, Heine M, Schuler G, Romani N (1993) Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. J Clin Invest 92:2587–2596

    Article  PubMed  CAS  Google Scholar 

  9. Stingl G, Tamaki K, Katz SI (1980) Origin and function of epidermal Langerhans cells. Immunol Rev 53:149–174

    Article  PubMed  CAS  Google Scholar 

  10. Grabbe S, Steinert M, Mahnke K, Schwartz A, Luger TA, Schwarz T (1996) Dissection of antigenic and irritative effects of epicutaneously applied haptens in mice. Evidence that not the antigenic component but nonspecific proinflammatory effects of haptens determine the concentration-dependent elicitation of allergic contact dermatitis. J Clin Invest 98:1158–1164

    Article  PubMed  CAS  Google Scholar 

  11. Griffiths CE, Dearman RJ, Cumberbatch M, Kimber I (2005) Cytokines and Langerhans cell mobilisation in mouse and man. Cytokine 32:67–70

    Article  PubMed  CAS  Google Scholar 

  12. Martinon F, Agostini L, Meylan E, Tschopp J (2004) Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol 14:1929–1934

    Article  PubMed  CAS  Google Scholar 

  13. Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD (2007) The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol 17:1140–1145

    Article  PubMed  CAS  Google Scholar 

  14. Grabbe S, Schwarz T (1998) Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today 19:37–44

    Article  PubMed  CAS  Google Scholar 

  15. Allenby CF, Basketter DA (1993) An arm immersion model of compromised skin (II). Influence on minimal eliciting patch test concentrations of nickel. Contact Dermatitis 28:129–133

    Article  PubMed  CAS  Google Scholar 

  16. Cumberbatch M, Scott RC, Basketter DA, Scholes EW, Hilton J, Dearman RJ, Kimber I (1993) Influence of sodium lauryl sulphate on 2,4-dinitrochlorobenzene-induced lymph node activation. Toxicology 77:181–191

    Article  PubMed  CAS  Google Scholar 

  17. Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, Bertin J, Coyle AJ, Galan JE, Askenase PW et al (2006) Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24:317–327

    Article  PubMed  CAS  Google Scholar 

  18. Watanabe H, Gehrke S, Contassot E, Roques S, Tschopp J, Friedmann PS, French LE, Gaide O (2008) Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. J Immunol 180:5826–5832

    PubMed  CAS  Google Scholar 

  19. Terheyden P, Kortum AK, Schulze HJ, Durani B, Remling R, Mauch C, Junghans V, Schadendorf D, Beiteke U, Junger M et al (2007) Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group. J Cancer Res Clin Oncol 133:437–444

    Article  PubMed  CAS  Google Scholar 

  20. Yoo J, Omori M, Gyarmati D, Zhou B, Aye T, Brewer A, Comeau MR, Campbell DJ, Ziegler SF (2005) Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med 202:541–549

    Article  PubMed  CAS  Google Scholar 

  21. Granstein RD, Sauder DN (1987) Whole-body exposure to ultraviolet radiation results in increased serum interleukin-1 activity in humans. Lymphokine Res 6:187–193

    PubMed  CAS  Google Scholar 

  22. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 11:136–140

    Article  PubMed  CAS  Google Scholar 

  23. Pickard C, Louafi F, McGuire C, Lowings K, Kumar P, Cooper H, Dearman RJ, Cumberbatch M, Kimber I, Healy E et al (2009) The cutaneous biochemical redox barrier: a component of the innate immune defenses against sensitization by highly reactive environmental xenobiotics. J Immunol 183:7576–7584

    Article  PubMed  CAS  Google Scholar 

  24. Naughton GK, Eisinger M, Bystryn JC (1983) Antibodies to normal human melanocytes in vitiligo. J Exp Med 158:246–251

    Article  PubMed  CAS  Google Scholar 

  25. Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK (1996) Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol 148:1219–1228

    PubMed  Google Scholar 

  26. Sehgal VN, Srivastava G (2006) Vitiligo: auto-immunity and immune responses. Int J Dermatol 45:583–590

    Article  PubMed  Google Scholar 

  27. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G, Bennett DC, Fain PR, Spritz RA (2007) NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 356:1216–1225

    Article  PubMed  CAS  Google Scholar 

  28. Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature 434:926–933

    Article  PubMed  CAS  Google Scholar 

  29. O’Sullivan BJ, Thomas HE, Pai S, Santamaria P, Iwakura Y, Steptoe RJ, Kay TW, Thomas R (2006) IL-1 beta breaks tolerance through expansion of CD25+ effector T cells. J Immunol 176:7278–7287

    PubMed  Google Scholar 

  30. Gauthier Y, Cario-Andre M, Lepreux S, Pain C, Taieb A (2003) Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo. Br J Dermatol 148:95–101

    Article  PubMed  CAS  Google Scholar 

  31. Ting JP, Kastner DL, Hoffman HM (2006) CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 6:183–195

    Article  PubMed  CAS  Google Scholar 

  32. Hoffman HM (2010) The registry of NLRP3 sequence variants http://fmf.igh.cnrs.fr/ISSAID/infevers/

  33. Hawkins PN, Lachmann HJ, McDermott MF (2003) Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med 348:2583–2584

    Article  PubMed  Google Scholar 

  34. Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL, Anderson JP, Wanderer AA, Firestein GS (2004) Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 364:1779–1785

    Article  PubMed  CAS  Google Scholar 

  35. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E et al (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 355:581–592

    Article  PubMed  CAS  Google Scholar 

  36. Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, Nunez G, Matsue H (2009) Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. J Exp Med 206:1037–1046

    Article  PubMed  CAS  Google Scholar 

  37. McCulloch CA, Downey GP, El-Gabalawy H (2006) Signalling platforms that modulate the inflammatory response: new targets for drug development. Nat Rev Drug Discov 5:864–876

    Article  PubMed  CAS  Google Scholar 

  38. Kallinich T, Haffner D, Niehues T, Huss K, Lainka E, Neudorf U, Schaefer C, Stojanov S, Timmann C, Keitzer R et al (2007) Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics 119:e474–e483

    Article  PubMed  Google Scholar 

  39. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241

    Article  PubMed  CAS  Google Scholar 

  40. Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, Kastner DL (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci USA 100:13501–13506

    Article  PubMed  CAS  Google Scholar 

  41. Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, McCormick M, Zhang Z, Alnemri ES (2007) Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell 28:214–227

    Article  PubMed  CAS  Google Scholar 

  42. Katayama T, Tachinami K, Ishiguro M, Kubota Y (1994) The relation between Behcet’s disease and interleukin-1 beta production. Nippon Ganka Gakkai Zasshi 98:197–201

    PubMed  CAS  Google Scholar 

  43. Yosipovitch G, Shohat B, Bshara J, Wysenbeek A, Weinberger A (1995) Elevated serum interleukin 1 receptors and interleukin 1B in patients with Behcet’s disease: correlations with disease activity and severity. Isr J Med Sci 31:345–348

    PubMed  CAS  Google Scholar 

  44. Botsios C, Sfriso P, Furlan A, Punzi L, Dinarello CA (2008) Resistant Behcet disease responsive to anakinra. Ann Intern Med 149:284–286

    PubMed  Google Scholar 

  45. Mamula P, Markowitz JE, Baldassano RN (2003) Inflammatory bowel disease in early childhood and adolescence: special considerations. Gastroenterol Clin North Am 32:967–995, viii

    Article  PubMed  Google Scholar 

  46. Eckmann L, Karin M (2005) NOD2 and Crohn’s disease: loss or gain of function? Immunity 22:661–667

    Article  PubMed  CAS  Google Scholar 

  47. Villani AC, Lemire M, Fortin G, Louis E, Silverberg MS, Collette C, Baba N, Libioulle C, Belaiche J, Bitton A et al (2009) Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet 41:71–76

    Article  PubMed  CAS  Google Scholar 

  48. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521

    Article  PubMed  CAS  Google Scholar 

  49. So A, De Smedt T, Revaz S, Tschopp J (2007) A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 9:R28

    Article  PubMed  Google Scholar 

  50. McGonagle D, Tan AL, Shankaranarayana S, Madden J, Emery P, McDermott MF (2007) Management of treatment resistant inflammation of acute on chronic tophaceous gout with anakinra. Ann Rheum Dis 66:1683–1684

    Article  PubMed  CAS  Google Scholar 

  51. von Andrian UH, Mackay CR (2000) T-cell function and migration. Two sides of the same coin. N Engl J Med 343:1020–1034

    Article  Google Scholar 

  52. Liu L, Fuhlbrigge RC, Karibian K, Tian T, Kupper TS (2006) Dynamic programming of CD8+ T cell trafficking after live viral immunization. Immunity 25:511–520

    Article  PubMed  CAS  Google Scholar 

  53. Spreafico R, Ricciardi-Castagnoli P, Mortellaro A (2010) The controversial relationship between NLRP3, alum, danger signals and the next-generation adjuvants. Eur J Immunol 40:638–642

    Article  PubMed  CAS  Google Scholar 

  54. Li H, Nookala S, Re F (2007) Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol 178:5271–5276

    PubMed  CAS  Google Scholar 

  55. Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, Bergen IM, Castillo R, Lambrecht BN, Tschopp J (2008) Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 181:3755–3759

    PubMed  CAS  Google Scholar 

  56. Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA (2008) Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122–1126

    Article  PubMed  CAS  Google Scholar 

  57. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856

    Article  PubMed  CAS  Google Scholar 

  58. Franchi L, Nunez G (2008) The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol 38:2085–2089

    Article  PubMed  CAS  Google Scholar 

  59. McKee AS, Munks MW, MacLeod MK, Fleenor CJ, Van Rooijen N, Kappler JW, Marrack P (2009) Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol 183:4403–4414

    Article  PubMed  CAS  Google Scholar 

  60. Liu L, Zhong Q, Tian T, Dubin K, Athale SK, Kupper TS (2010) Epidermal injury and infection during poxvirus immunization is crucial for the generation of highly protective T cell-mediated immunity. Nat Med 16:224–227

    Article  PubMed  CAS  Google Scholar 

  61. Delaloye J, Roger T, Steiner-Tardivel QG, Le Roy D, Knaup Reymond M, Akira S, Petrilli V, Gomez CE, Perdiguero B, Tschopp J et al (2009) Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome. PLoS Pathog 5:e1000480

    Article  PubMed  Google Scholar 

  62. Dinarello CA (1998) Interleukin-1 beta, interleukin-18, and the interleukin-1 beta converting enzyme. Ann N Y Acad Sci 856:1–11

    Article  PubMed  CAS  Google Scholar 

  63. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS, Flavell RA (1995) Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science 267:2000–2003

    Article  PubMed  CAS  Google Scholar 

  64. Li P, Allen H, Banerjee S, Franklin S, Herzog L, Johnston C, McDowell J, Paskind M, Rodman L, Salfeld J et al (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80:401–411

    Article  PubMed  CAS  Google Scholar 

  65. Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A, Quintal L, Sekut L, Talanian R, Paskind M et al (1997) Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386:619–623

    Article  PubMed  CAS  Google Scholar 

  66. Dunne A, O’Neill LA (2003) The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003:re3

    Article  PubMed  Google Scholar 

  67. Dinarello CA (2004) Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 10:201–222

    PubMed  CAS  Google Scholar 

  68. Boraschi D, Dinarello CA (2006) IL-18 in autoimmunity: review. Eur Cytokine Netw 17:224–252

    PubMed  CAS  Google Scholar 

  69. Numerof RP, Asadullah K (2006) Cytokine and anti-cytokine therapies for psoriasis and atopic dermatitis. BioDrugs 20:93–103

    Article  PubMed  CAS  Google Scholar 

  70. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490

    Article  PubMed  CAS  Google Scholar 

  71. Palmer G, Lipsky BP, Smithgall MD, Meininger D, Siu S, Talabot-Ayer D, Gabay C, Smith DE (2008) The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33. Cytokine 42:358–364

    Article  PubMed  CAS  Google Scholar 

  72. Boraschi D, Tagliabue A (2006) The interleukin-1 receptor family. Vitam Horm 74:229–254

    Article  PubMed  CAS  Google Scholar 

  73. Dinarello CA (2005) An IL-1 family member requires caspase-1 processing and signals through the ST2 receptor. Immunity 23:461–462

    Article  PubMed  CAS  Google Scholar 

  74. Cornelis S, Kersse K, Festjens N, Lamkanfi M, Vandenabeele P (2007) Inflammatory caspases: targets for novel therapies. Curr Pharm Des 13:365–383

    Article  Google Scholar 

  75. Stack JH, Beaumont K, Larsen PD, Straley KS, Henkel GW, Randle JC, Hoffman HM (2005) IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients. J Immunol 175:2630–2634

    PubMed  CAS  Google Scholar 

  76. Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J (2007) A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol 8:497–503

    Article  PubMed  CAS  Google Scholar 

  77. Holzer AM, Kaplan LL, Levis WR (2006) Haptens as drugs: contact allergens are powerful topical immunomodulators. J Drugs Dermatol 5:410–416

    PubMed  Google Scholar 

  78. Berman B, Perez OA, Zell D (2006) Immunological strategies to fight skin cancer. Skin Therapy Lett 11:1–7

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology-Venereology, Geneva University, Rue Michel-Servet 1, 1211, Geneva, Switzerland

    Olivier Gaide

  2. Department of Pathology-Immunology, Geneva University, Rue Michel-Servet 1, 1211, Geneva, Switzerland

    Olivier Gaide

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  1. Olivier Gaide
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Correspondence to Olivier Gaide .

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Editors and Affiliations

  1. Institut de Transgénose, Labo. d'Immunologie et, CNRS, rue de la Férollerie 3B, Orléans CX 2, 45071, France

    Isabelle Couillin

  2. CNRS UMR 5201, Labo. Génétique et Cancer, Université de Lyon I, rue Laënnec 28, Lyon, 69008, France

    Virginie Pétrilli

  3. Dept. Immunology & Infectious, Diseases, Harvard School of Public Health, Huntington Ave. 651, Boston, 02115-6017, Massachusetts, USA

    Fabio Martinon

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Gaide, O. (2011). Inflammasome in the Skin. In: Couillin, I., Pétrilli, V., Martinon, F. (eds) The Inflammasomes. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0148-5_9

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  • DOI: https://doi.org/10.1007/978-3-0348-0148-5_9

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