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Annual Review of Pathology: Mechanisms of Disease

Volume 10, 2015

The Inflammasomes and Autoinflammatory Syndromes

Abstract

Inflammation, a vital response of the immune system to infection and damage to tissues, can be initiated by various germline-encoded innate immune-signaling receptors. Among these, the inflammasomes are critical for activation of the potent proinflammatory interleukin-1 cytokine family. Additionally, inflammasomes can trigger and maintain inflammatory responses aimed toward excess nutrients and the numerous danger signals that appear in a variety of chronic inflammatory diseases. We discuss our understanding of how inflammasomes assemble to trigger caspase-1 activation and subsequent cytokine release, describe how genetic mutations in inflammasome-related genes lead to autoinflammatory syndromes, and review the contribution of inflammasome activation to various pathologies arising from metabolic dysfunction. Insights into the mechanisms that govern inflammasome activation will help in the development of novel therapeutic strategies, not only for managing genetic diseases associated with overactive inflammasomes, but also for treating common metabolic diseases for which effective therapies are currently lacking.

Keyword(s): AIM2, ASC, CAPS, FMF, inflammasomes, NLRC4, NLRP1, NLRP12, NLRP3, NLRP6
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/content/journals/10.1146/annurev-pathol-012414-040431
2015-01-24
2024-04-18
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Literature Cited

  1. Medzhitov R. 1.  2008. Origin and physiological roles of inflammation. Nature 454:428–35 [Google Scholar]
  2. Henao-Mejia J, Elinav E, Thaiss CA, Flavell RA. 2.  2014. Inflammasomes and metabolic disease. Annu. Rev. Physiol. 76:57–78 [Google Scholar]
  3. Latz E, Xiao TS, Stutz A. 3.  2013. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13:397–411 [Google Scholar]
  4. von Moltke J, Ayres JS, Kofoed EM, Chavarria-Smith J, Vance RE. 4.  2013. Recognition of bacteria by inflammasomes. Annu. Rev. Immunol. 31:73–106 [Google Scholar]
  5. Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES. 5.  2002. The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J. Biol. Chem. 277:21119–22 [Google Scholar]
  6. Keller M, Ruegg A, Werner S, Beer HD. 6.  2008. Active caspase-1 is a regulator of unconventional protein secretion. Cell 132:818–31 [Google Scholar]
  7. Fink SL, Cookson BT. 7.  2005. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73:1907–16 [Google Scholar]
  8. Martinon F, Burns K, Tschopp J. 8.  2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417–26First evidence that inflammasomes assemble to form large multimolecular complexes. [Google Scholar]
  9. Park HH, Logette E, Raunser S, Cuenin S, Walz T. 9.  et al. 2007. Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex. Cell 128:533–46 [Google Scholar]
  10. Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC. 10.  et al. 2010. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat. Struct. Mol. Biol. 17:1324–29 [Google Scholar]
  11. Lin SC, Lo YC, Wu H. 11.  2010. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 465:885–90 [Google Scholar]
  12. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. 12.  2011. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 146:448–61 [Google Scholar]
  13. Siegel RM, Martin DA, Zheng L, Ng SY, Bertin J. 13.  et al. 1998. Death-effector filaments: novel cytoplasmic structures that recruit caspases and trigger apoptosis. J. Cell Biol. 141:1243–53 [Google Scholar]
  14. Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B. 14.  et al. 2007. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 14:1590–604 [Google Scholar]
  15. Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T. 15.  et al. 1999. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J. Biol. Chem. 274:33835–38Identification of ASC as a protein that forms insoluble aggregates upon activation. [Google Scholar]
  16. Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK. 16.  et al. 2014. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 156:1193–206Identification of the helical assembly of ASC into fibrils after activation by NLRP3 or AIM2. [Google Scholar]
  17. Cai X, Chen J, Xu H, Liu S, Jiang QX. 17.  et al. 2014. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156:1207–22 [Google Scholar]
  18. Wu H. 18.  2013. Higher-order assemblies in a new paradigm of signal transduction. Cell 153:287–92 [Google Scholar]
  19. Baroja-Mazo A, Martin-Sanchez F, Gomez AI, Martinez CM, Amores-Iniesta J. 19.  et al. 2014. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat. Immunol. 15:8738–4819, 20. Identification of the extracellular function of ASC and a novel form of cell-to-cell communication. [Google Scholar]
  20. Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A. 20.  et al. 2014. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat. Immunol 15:8727–3719, 20. Identification of the extracellular function of ASC and a novel form of cell-to-cell communication. [Google Scholar]
  21. Brydges S, Kastner DL. 21.  2006. The systemic autoinflammatory diseases: inborn errors of the innate immune system. Curr. Top. Microbiol. Immunol. 305:127–60 [Google Scholar]
  22. 22. French FMF Consort 1997. A candidate gene for familial Mediterranean fever. Nat. Genet. 17:25–31 [Google Scholar]
  23. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. 23.  2001. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome. Nat. Genet. 29:301–5Discovery that point mutations in NLRP3 cause autoinflammatory syndromes. [Google Scholar]
  24. Hoffman HM, Wanderer AA, Broide DH. 24.  2001. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J. Allergy Clin. Immunol. 108:615–20 [Google Scholar]
  25. 25. Int. FMF Consort 1997. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90:797–807 [Google Scholar]
  26. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW. 26.  et al. 1999. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–44 [Google Scholar]
  27. Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H. 27.  et al. 2008. The Infevers autoinflammatory mutation online registry: update with new genes and functions. Hum. Mutat. 29:803–8 [Google Scholar]
  28. Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J. 28.  et al. 2007. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 56:1273–85 [Google Scholar]
  29. Dowds TA, Masumoto J, Chen FF, Ogura Y, Inohara N, Nunez G. 29.  2003. Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product. Biochem. Biophys. Res. Commun. 302:575–80 [Google Scholar]
  30. Duncan JA, Bergstralh DT, Wang Y, Willingham SB, Ye Z. 30.  et al. 2007. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. PNAS 104:8041–46 [Google Scholar]
  31. O'Connor W Jr, Harton JA, Zhu X, Linhoff MW, Ting JP. 31.  2003. Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-κB suppressive properties. J. Immunol. 171:6329–33 [Google Scholar]
  32. Willingham SB, Allen IC, Bergstralh DT, Brickey WJ, Huang MT. 32.  et al. 2009. NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J. Immunol. 183:2008–15 [Google Scholar]
  33. Willingham SB, Bergstralh DT, O'Connor W, Morrison AC, Taxman DJ. 33.  et al. 2007. Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC. Cell Host Microbe 2:147–59 [Google Scholar]
  34. Yu JW, Wu J, Zhang Z, Datta P, Ibrahimi I. 34.  et al. 2006. Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization. Cell Death Differ. 13:236–49 [Google Scholar]
  35. Verma D, Lerm M, Blomgran Julinder R, Eriksson P, Soderkvist P, Sarndahl E. 35.  2008. Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases?. Arthritis Rheum. 58:888–94 [Google Scholar]
  36. Nakagawa K, Gonzalez-Roca E, Souto A, Kawai T, Umebayashi H. 36.  et al. 2013. Somatic NLRP3 mosaicism in Muckle–Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes. Ann. Rheum. Dis. In press. doi: 10.1136/annrheumdis-2013-204361
  37. Saito M, Nishikomori R, Kambe N, Fujisawa A, Tanizaki H. 37.  et al. 2008. Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients. Blood 111:2132–41 [Google Scholar]
  38. Brydges SD, Mueller JL, McGeough MD, Pena CA, Misaghi A. 38.  et al. 2009. Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity. Immunity 30:6875–87 [Google Scholar]
  39. Rosengren S, Mueller JL, Anderson JP, Niehaus BL, Misaghi A. 39.  et al. 2007. Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermia. J. Allergy Clin. Immunol. 119:991–96 [Google Scholar]
  40. Stack JH, Beaumont K, Larsen PD, Straley KS, Henkel GW. 40.  et al. 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. 175:2630–34 [Google Scholar]
  41. Haverkamp MH, van de Vosse E, Goldbach-Mansky R, Holland SM. 41.  2014. Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS). Clin. Exp. Immunol. 177:3720–31 [Google Scholar]
  42. Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J. 42.  et al. 2004. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 364:1779–85 [Google Scholar]
  43. Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K. 43.  et al. 2009. In vivo regulation of interleukin 1β in patients with cryopyrin-associated periodic syndromes. J. Exp. Med. 206:1029–36 [Google Scholar]
  44. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J. 44.  et al. 2006. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N. Engl. J. Med. 355:581–9244–46. Demonstration of the clinical efficacy of IL-1 therapy in treating CAPS. [Google Scholar]
  45. Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ. 45.  et al. 2008. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 58:2443–5244–46. Demonstration of the clinical efficacy of IL-1 therapy in treating CAPS. [Google Scholar]
  46. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E. 46.  et al. 2009. Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360:2416–2544–46. Demonstration of the clinical efficacy of IL-1 therapy in treating CAPS. [Google Scholar]
  47. Meng G, Zhang F, Fuss I, Kitani A, Strober W. 47.  2009. A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30:860–74 [Google Scholar]
  48. Nakamura Y, Franchi L, Kambe N, Meng G, Strober W, Nunez G. 48.  2012. Critical role for mast cells in interleukin-1β-driven skin inflammation associated with an activating mutation in the Nlrp3 protein. Immunity 37:85–95 [Google Scholar]
  49. Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG. 49.  et al. 2009. Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. J. Exp. Med. 206:1037–46 [Google Scholar]
  50. Brydges SD, Broderick L, McGeough MD, Pena CA, Mueller JL, Hoffman HM. 50.  2013. Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. J. Clin. Investig. 123:4695–705 [Google Scholar]
  51. Centola M, Wood G, Frucht DM, Galon J, Aringer M. 51.  et al. 2000. The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators. Blood 95:3223–31 [Google Scholar]
  52. Diaz A, Hu C, Kastner DL, Schaner P, Reginato AM. 52.  et al. 2004. Lipopolysaccharide-induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts: a prominent splice isoform lacks the C-terminal domain that is highly mutated in familial Mediterranean fever. Arthritis Rheum. 50:3679–89 [Google Scholar]
  53. Matzner Y, Abedat S, Shapiro E, Eisenberg S, Bar-Gil-Shitrit A. 53.  et al. 2000. Expression of the familial Mediterranean fever gene and activity of the C5a inhibitor in human primary fibroblast cultures. Blood 96:727–31 [Google Scholar]
  54. Papin S, Cazeneuve C, Duquesnoy P, Jeru I, Sahali D, Amselem S. 54.  2003. The tumor necrosis factor α-dependent activation of the human Mediterranean fever (MEFV) promoter is mediated by a synergistic interaction between C/EBPβ and NFκB p65. J. Biol. Chem. 278:48839–47 [Google Scholar]
  55. Chae JJ, Komarow HD, Cheng J, Wood G, Raben N. 55.  et al. 2003. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol. Cell 11:591–604 [Google Scholar]
  56. Masumoto J, Dowds TA, Schaner P, Chen FF, Ogura Y. 56.  et al. 2003. ASC is an activating adaptor for NF-κB and caspase-8-dependent apoptosis. Biochem. Biophys. Res. Commun. 303:69–73 [Google Scholar]
  57. Richards N, Schaner P, Diaz A, Stuckey J, Shelden E. 57.  et al. 2001. Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. J. Biol. Chem. 276:39320–29 [Google Scholar]
  58. Waite AL, Schaner P, Hu C, Richards N, Balci-Peynircioglu B. 58.  et al. 2009. Pyrin and ASC co-localize to cellular sites that are rich in polymerizing actin. Exp. Biol. Med. 234:40–52 [Google Scholar]
  59. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. 59.  2004. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle–Wells autoinflammatory disorder. Immunity 20:319–25 [Google Scholar]
  60. Martinon F, Tschopp J. 60.  2004. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117:561–74 [Google Scholar]
  61. Stehlik C, Lee SH, Dorfleutner A, Stassinopoulos A, Sagara J, Reed JC. 61.  2003. Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation. J. Immunol. 171:6154–63 [Google Scholar]
  62. Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S. 62.  et al. 2002. PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-κB and caspase-1-dependent cytokine processing. J. Biol. Chem. 277:29874–80 [Google Scholar]
  63. Stehlik C, Fiorentino L, Dorfleutner A, Bruey JM, Ariza EM. 63.  et al. 2002. The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor κB activation pathways. J. Exp. Med. 196:1605–15 [Google Scholar]
  64. Kees S, Langevitz P, Zemer D, Padeh S, Pras M, Livneh A. 64.  1997. Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF). Q. J. Med. 90:643–47 [Google Scholar]
  65. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O. 65.  et al. 2005. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 84:1–11 [Google Scholar]
  66. Tutar E, Yalcinkaya F, Ozkaya N, Ekim M, Atalay S. 66.  2003. Incidence of pericardial effusion during attacks of familial Mediterranean fever. Heart 89:1257–58 [Google Scholar]
  67. Zimand S, Tauber T, Hegesch T, Aladjem M. 67.  1994. Familial Mediterranean fever presenting with massive cardiac tamponade. Clin. Exp. Rheumatol. 12:67–69 [Google Scholar]
  68. Livneh A, Madgar I, Langevitz P, Zemer D. 68.  1994. Recurrent episodes of acute scrotum with ischemic testicular necrosis in a patient with familial Mediterranean fever. J. Urol. 151:431–32 [Google Scholar]
  69. Majeed HA, Ghandour K, Shahin HM. 69.  2000. The acute scrotum in Arab children with familial Mediterranean fever. Pediatr. Surg. Int. 16:72–74 [Google Scholar]
  70. Heller H, Gafni J, Michaeli D, Shahin N, Sohar E. 70.  et al. 1966. The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum. 9:1–17 [Google Scholar]
  71. Azizi E, Fisher BK. 71.  1976. Cutaneous manifestations of familial Mediterranean fever. Arch. Dermatol. 112:364–66 [Google Scholar]
  72. Barzilai A, Langevitz P, Goldberg I, Kopolovic J, Livneh A. 72.  et al. 2000. Erysipelas-like erythema of familial Mediterranean fever: clinicopathologic correlation. J. Am. Acad. Dermatol. 42:791–95 [Google Scholar]
  73. 73. Int. Soc. Syst. Auto-Inflamm. Dis 2013. Infevers: an online database for autoinflammatory mutations. Updated July 31. http://fmf.igh.cnrs.fr/ISSAID/infevers/
  74. Milhavet F, Cuisset L, Hoffman H, El-Shanti H, Slim R. 74.  et al. 2008. The Infevers autoinflammatory mutation online registry: update with new genes and functions. Hum. Mutat. 29:803–8 [Google Scholar]
  75. Toutiou I, Lesage S, McDermott M, Cuisset L, Hoffman H. 75.  et al. 2004. Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum. Mutat. 24:194–98 [Google Scholar]
  76. Sarrauste de Menthière C, Terrière S, Pugnère D, Ruiz M, Demaille J, Touitou I. 76.  2003. INFEVERS: the registry for FMF and hereditary inflammatory disorders mutations. Nucleic Acids Res 31:282–85 [Google Scholar]
  77. Akar N, Misiroglu M, Yalcinkaya F, Akar E, Cakar N. 77.  et al. 2000. MEFV mutations in Turkish patients suffering from familial Mediterranean fever. Hum. Mutat. 15:118–19 [Google Scholar]
  78. Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E. 78.  et al. 1999. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am. J. Hum. Genet. 64:949–62 [Google Scholar]
  79. Cazeneuve C, Sarkisian T, Pecheux C, Dervichian M, Nedelec B. 79.  et al. 1999. MEFV-gene analysis in Armenian patients with familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype—genetic and therapeutic implications. Am. J. Hum. Genet. 65:88–97 [Google Scholar]
  80. Mansour I, Delague V, Cazeneuve C, Dode C, Chouery E. 80.  et al. 2001. Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek Catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations. Eur. J. Hum. Genet. 9:51–55 [Google Scholar]
  81. Medlej-Hashim M, Rawashdeh M, Chouery E, Mansour I, Delague V. 81.  et al. 2000. Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients. Hum. Mutat. 15:384 [Google Scholar]
  82. Padeh S, Shinar Y, Pras E, Zemer D, Langevitz P. 82.  et al. 2003. Clinical and diagnostic value of genetic testing in 216 Israeli children with familial Mediterranean fever. J. Rheumatol. 30:185–90 [Google Scholar]
  83. Akarsu AN, Saatci U, Ozen S, Bakkaloglu A, Besbas N, Sarfarazi M. 83.  1997. Genetic linkage study of familial Mediterranean fever (FMF) to 16p13.3 and evidence for genetic heterogeneity in the Turkish population. J. Med. Genet. 34:573–78 [Google Scholar]
  84. Domingo C, Touitou I, Bayou A, Ozen S, Notarnicola C. 84.  et al. 2000. Familial Mediterranean fever in the ‘Chuetas’ of Mallorca: a question of Jewish origin or genetic heterogeneity. Eur. J. Hum. Genet. 8:242–46 [Google Scholar]
  85. Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A. 85.  et al. 2000. The genetic basis of autosomal dominant familial Mediterranean fever. Q. J. Med. 93:217–21 [Google Scholar]
  86. Tennent GA, Lovat LB, Pepys MB. 86.  1995. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. PNAS 92:4299–303 [Google Scholar]
  87. Balci-Peynircioglu B, Waite AL, Schaner P, Taskiran ZE, Richards N. 87.  et al. 2008. Expression of ASC in renal tissues of familial Mediterranean fever patients with amyloidosis: postulating a role for ASC in AA type amyloid deposition. Exp. Biol. Med. 233:1324–33 [Google Scholar]
  88. Gavrilin MA, Mitra S, Seshadri S, Nateri J, Berhe F. 88.  et al. 2009. Pyrin critical to macrophage IL-1β response to Francisella challenge. J. Immunol. 182:7982–89 [Google Scholar]
  89. Papin S, Cuenin S, Agostini L, Martinon F, Werner S. 89.  et al. 2007. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1β processing. Cell Death Differ. 14:1457–66 [Google Scholar]
  90. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT. 90.  et al. 2008. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-κB through its N-terminal fragment. Blood 112:1794–803 [Google Scholar]
  91. Hesker PR, Nguyen M, Kovarova M, Ting JP, Koller BH. 91.  2012. Genetic loss of murine pyrin, the Familial Mediterranean Fever protein, increases interleukin-1β levels. PLOS ONE 7:e51105 [Google Scholar]
  92. Chae JJ, Cho YH, Lee GS, Cheng J, Liu PP. 92.  et al. 2011. Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in mice. Immunity 34:755–68 [Google Scholar]
  93. Misawa T, Takahama M, Kozaki T, Lee H, Zou J. 93.  et al. 2013. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14:454–60 [Google Scholar]
  94. Balci-Peynircioglu B, Waite AL, Hu C, Richards N, Staubach-Grosse A. 94.  et al. 2008. Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva. J. Cell Physiol. 216:595–602 [Google Scholar]
  95. Taskiran EZ, Cetinkaya A, Balci-Peynircioglu B, Akkaya YZ, Yilmaz E. 95.  2012. The effect of colchicine on pyrin and pyrin interacting proteins. J. Cell. Biochem. 113:3536–46 [Google Scholar]
  96. Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L. 96.  et al. 2007. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J. Histochem. Cytochem. 55:443–52 [Google Scholar]
  97. Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G. 97.  et al. 2007. NALP1 in vitiligo-associated multiple autoimmune disease. N. Engl. J. Med. 356:1216–25 [Google Scholar]
  98. Magitta NF, Boe Wolff AS, Johansson S, Skinningsrud B, Lie BA. 98.  et al. 2009. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes. Genes Immun. 10:120–24 [Google Scholar]
  99. Pontillo A, Vendramin A, Catamo E, Fabris A, Crovella S. 99.  2011. The missense variation Q705K in CIAS1/NALP3/NLRP3 gene and an NLRP1 haplotype are associated with celiac disease. Am. J. Gastroenterol 106:539–44 [Google Scholar]
  100. Dieude P, Guedj M, Wipff J, Ruiz B, Riemekasten G. 100.  et al. 2011. NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis. Ann. Rheum. Dis. 70:668–74 [Google Scholar]
  101. Finger JN, Lich JD, Dare LC, Cook MN, Brown KK. 101.  et al. 2012. Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity. J. Biol. Chem. 287:25030–37 [Google Scholar]
  102. Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S. 102.  et al. 2013. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. PNAS 110:2952–56 [Google Scholar]
  103. Okada K, Hirota E, Mizutani Y, Fujioka T, Shuin T. 103.  et al. 2004. Oncogenic role of NALP7 in testicular seminomas. Cancer Sci. 95:949–54 [Google Scholar]
  104. Khare S, Dorfleutner A, Bryan NB, Yun C, Radian AD. 104.  et al. 2012. An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity 36:464–76 [Google Scholar]
  105. Hodges MD, Rees HC, Seckl MJ, Newlands ES, Fisher RA. 105.  2003. Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J. Med. Genet. 40:e95
  106. Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R. 106.  1999. Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum. Mol. Genet. 8:667–71 [Google Scholar]
  107. Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R. 107.  et al. 2006. Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat. Genet. 38:300–2 [Google Scholar]
  108. Sensi A, Gualandi F, Pittalis MC, Calabrese O, Falciano F. 108.  et al. 2000. Mole maker phenotype: possible narrowing of the candidate region. Eur. J. Hum. Genet. 8:641–44 [Google Scholar]
  109. Wang CM, Dixon PH, Decordova S, Hodges MD, Sebire NJ. 109.  et al. 2009. Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region. J. Med. Genet. 46:569–75 [Google Scholar]
  110. Mahadevan S, Wen S, Wan YW, Peng HH, Otta S. 110.  et al. 2014. NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation. Hum. Mol. Genet. 23:706–16 [Google Scholar]
  111. Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW. 111.  et al. 2006. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nat. Immunol. 7:569–75 [Google Scholar]
  112. Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG. 112.  et al. 2010. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. PNAS 107:3076–80 [Google Scholar]
  113. Lightfield KL, Persson J, Trinidad NJ, Brubaker SW, Kofoed EM. 113.  et al. 2011. Differential requirements for NAIP5 in activation of the NLRC4 inflammasome. Infect. Immun. 79:1606–14 [Google Scholar]
  114. Tenthorey JL, Kofoed EM, Daugherty MD, Malik HS, Vance RE. 114.  2014. Molecular basis for specific recognition of bacterial ligands by NAIP/NLRC4 inflammasomes. Mol. Cell 54:17–29 [Google Scholar]
  115. Zhao Y, Yang J, Shi J, Gong YN, Lu Q. 115.  et al. 2011. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477:596–600 [Google Scholar]
  116. Sutterwala FS, Flavell RA. 116.  2009. NLRC4/IPAF: a CARD carrying member of the NLR family. Clin. Immunol. 130:2–6 [Google Scholar]
  117. Canna S, de Jesus AA, Gouni S, Brooks SR, Marrero B. 117.  et al. 2014. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat. Genet. 46:1140–46 [Google Scholar]
  118. Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E. 118.  et al. 2014. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat. Genet 46:1135–39 [Google Scholar]
  119. Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G. 119.  et al. 2009. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10:266–72119–122. Discovery of the AIM2 inflammasome. [Google Scholar]
  120. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. 120.  2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509–13119–122. Discovery of the AIM2 inflammasome. [Google Scholar]
  121. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G. 121.  et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18119–122. Discovery of the AIM2 inflammasome. [Google Scholar]
  122. Schroder K, Muruve DA, Tschopp J. 122.  2009. Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome. Curr. Biol. 19:R262–65119–122. Discovery of the AIM2 inflammasome. [Google Scholar]
  123. Jin T, Perry A, Jiang J, Smith P, Curry JA. 123.  et al. 2012. Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity 36:561–71 [Google Scholar]
  124. Zhang W, Cai Y, Xu W, Yin Z, Gao X, Xiong S. 124.  2013. AIM2 facilitates the apoptotic DNA-induced systemic lupus erythematosus via arbitrating macrophage functional maturation. J. Clin. Immunol. 33:925–37 [Google Scholar]
  125. Dombrowski Y, Peric M, Koglin S, Kammerbauer C, Goss C. 125.  et al. 2011. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl. Med. 3:82ra38 [Google Scholar]
  126. Kopfnagel V, Wittmann M, Werfel T. 126.  2011. Human keratinocytes express AIM2 and respond to dsDNA with IL-1β secretion. Exp. Dermatol. 20:1027–29 [Google Scholar]
  127. Fiorentino L, Stehlik C, Oliveira V, Ariza ME, Godzik A, Reed JC. 127.  2002. A novel PAAD-containing protein that modulates NF-κB induction by cytokines tumor necrosis factor-α and interleukin-1β. J. Biol. Chem. 277:35333–40 [Google Scholar]
  128. Williams KL, Taxman DJ, Linhoff MW, Reed W, Ting JP-Y. 128.  2003. Cutting edge: Monarch-1: a pyrin/nucleotide-binding domain/leucine-rich repeat protein that controls classical and nonclassical MHC class I genes. J. Immunol. 170:5354–58 [Google Scholar]
  129. Jeru I, Duquesnoy P, Fernandes-Alnemri T, Cochet E, Yu JW. 129.  et al. 2008. Mutations in NALP12 cause hereditary periodic fever syndromes. PNAS 105:1614–19 [Google Scholar]
  130. Borghini S, Tassi S, Chiesa S, Caroli F, Carta S. 130.  et al. 2011. Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum. 63:830–39 [Google Scholar]
  131. Jeru I, Hentgen V, Normand S, Duquesnoy P, Cochet E. 131.  et al. 2011. Role of interleukin-1β in NLRP12-associated autoinflammatory disorders and resistance to anti-interleukin-1 therapy. Arthritis Rheum. 63:2142–48 [Google Scholar]
  132. Jeru I. Borgne G, Cochet E, Hayrapetyan H, Duquesnoy P. 132. , Le et al. 2011. Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis Rheum. 63:1459–64 [Google Scholar]
  133. Lich JD, Williams KL, Moore CB, Arthur JC, Davis BK. 133.  et al. 2007. Monarch-1 suppresses non-canonical NF-κB activation and p52-dependent chemokine expression in monocytes. J. Immunol. 178:1256–60 [Google Scholar]
  134. Chen GY, Liu M, Wang F, Bertin J, Nunez G. 134.  2011. A functional role for NLRP6 in intestinal inflammation and tumorigenesis. J. Immunol. 186:7187–94 [Google Scholar]
  135. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA. 135.  et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–57 [Google Scholar]
  136. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP. 136.  et al. 2014. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–59 [Google Scholar]
  137. Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J. 137.  et al. 2012. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488:389–93 [Google Scholar]
  138. Glorioso N, Herrera VL, Didishvili T, Ortu MF, Zaninello R. 138.  et al. 2013. Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population. PLOS ONE 8:e77562 [Google Scholar]
  139. Ting JP, Duncan JA, Lei Y. 139.  2010. How the noninflammasome NLRs function in the innate immune system. Science 327:286–90 [Google Scholar]
  140. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M. 140.  et al. 2000. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908:244–54 [Google Scholar]
  141. Troen BR. 141.  2003. The biology of aging. Mt. Sinai J. Med. 70:3–22 [Google Scholar]
  142. Gregor MF, Hotamisligil GS. 142.  2011. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29:415–45 [Google Scholar]
  143. Nuki G, Simkin PA. 143.  2006. A concise history of gout and hyperuricemia and their treatment. Arthritis Res. Ther. 8:Suppl. 1S1 [Google Scholar]
  144. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. 144.  2014. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann. Rheum. Dis. In press. doi: 10.1136/annrheumdis-2013-204463
  145. Shi Y, Evans JE, Rock KL. 145.  2003. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–21 [Google Scholar]
  146. Rees F, Hui M, Doherty M. 146.  2014. Optimizing current treatment of gout. Nat. Rev. Rheumatol. 10:271–83 [Google Scholar]
  147. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. 147.  2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–41Identification that the NLRP3 inflammasome recognizes gout-associated uric acid crystals. [Google Scholar]
  148. Schumacher HR Jr, Sundy JS, Terkeltaub R, Knapp HR, Mellis SJ. 148.  et al. 2012. Rilonacept (interleukin-1 Trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 64:876–84 [Google Scholar]
  149. So A, De Smedt T, Revaz S, Tschopp J. 149.  2007. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res. Ther. 9:R28 [Google Scholar]
  150. Kool M, Willart MA, van Nimwegen M, Bergen I, Pouliot P. 150.  et al. 2011. An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Immunity 34:527–40 [Google Scholar]
  151. 151. World Health Organ 2014. World Health Statistics 2014 Geneva: WHO Press http://www.who.int/gho/publications/world_health_statistics/2014/en/
  152. Lusis AJ. 152.  2000. Atherosclerosis. Nature 407:233–41 [Google Scholar]
  153. Wright SD, Burton C, Hernandez M, Hassing H, Montenegro J. 153.  et al. 2000. Infectious agents are not necessary for murine atherogenesis. J. Exp. Med. 191:1437–42 [Google Scholar]
  154. Grebe A, Latz E. 154.  2013. Cholesterol crystals and inflammation. Curr. Rheumatol. Rep. 15:313 [Google Scholar]
  155. Sheedy FJ, Grebe A, Rayner KJ, Kalantari P, Ramkhelawon B. 155.  et al. 2013. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14:812–20 [Google Scholar]
  156. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J. 156.  et al. 2010. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11:155–61 [Google Scholar]
  157. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G. 157.  et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–61157, 158. Identification of the role of NLRP3 in atherosclerosis. [Google Scholar]
  158. Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev AT. 158.  et al. 2011. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur. J. Immunol. 41:2040–51157, 158. Identification of the role of NLRP3 in atherosclerosis. [Google Scholar]
  159. Rajamaki K, Lappalainen J, Oorni K, Valimaki E, Matikainen S. 159.  et al. 2010. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLOS ONE 5:e11765 [Google Scholar]
  160. Gage J, Hasu M, Thabet M, Whitman SC. 160.  2012. Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice. Can. J. Cardiol. 28:222–29 [Google Scholar]
  161. Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A. 161.  et al. 2012. Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. Biochem. Biophys. Res. Commun. 425:162–68 [Google Scholar]
  162. Elhage R, Maret A, Pieraggi MT, Thiers JC, Arnal JF, Bayard F. 162.  1998. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Circulation 97:242–44 [Google Scholar]
  163. Olofsson PS, Sheikine Y, Jatta K, Ghaderi M, Samnegard A. 163.  et al. 2009. A functional interleukin-1 receptor antagonist polymorphism influences atherosclerosis development. The interleukin-1β:interleukin-1 receptor antagonist balance in atherosclerosis. Circ. J. 73:1531–36 [Google Scholar]
  164. De Nardo D, Latz E. 164.  2011. NLRP3 inflammasomes link inflammation and metabolic disease. Trends Immunol. 32:373–79 [Google Scholar]
  165. Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y. 165.  et al. 2013. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis. Nat. Immunol. 14:1045–53 [Google Scholar]
  166. Fettelschoss A, Kistowska M, LeibundGut-Landmann S, Beer HD, Johansen P. 166.  et al. 2011. Inflammasome activation and IL-1β target IL-1α for secretion as opposed to surface expression. PNAS 108:18055–60 [Google Scholar]
  167. Ridker PM, Howard CP, Walter V, Everett B, Libby P. 167.  et al. 2012. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation 126:2739–48 [Google Scholar]
  168. Ridker PM, Thuren T, Zalewski A, Libby P. 168.  2011. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am. Heart J. 162:597–605 [Google Scholar]
  169. Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T. 169.  et al. 2012. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J. Neuroinflamm. 9:151 [Google Scholar]
  170. Prinz M, Priller J, Sisodia SS, Ransohoff RM. 170.  2011. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neurosci. 14:1227–35 [Google Scholar]
  171. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG. 171.  et al. 2008. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat. Immunol. 9:857–65171, 172. Discovery that Aβ can trigger NLRP3 and identification of a role for NLRP3 in the pathology of Alzheimer's disease. [Google Scholar]
  172. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S. 172.  et al. 2013. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493:674–78171, 172. Discovery that Aβ can trigger NLRP3 and identification of a role for NLRP3 in the pathology of Alzheimer's disease. [Google Scholar]
  173. Youm YH, Grant RW, McCabe LR, Albarado DC, Nguyen KY. 173.  et al. 2013. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab. 18:519–32 [Google Scholar]
  174. Stienstra R, Joosten LA, Koenen T, van Tits B, van Diepen JA. 174.  et al. 2010. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 12:593–605 [Google Scholar]
  175. Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL. 175.  et al. 2011. Inflammasome is a central player in the induction of obesity and insulin resistance. PNAS 108:15324–29 [Google Scholar]
  176. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K. 176.  et al. 2011. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17:179–88 [Google Scholar]
  177. Wen H, Gris D, Lei Y, Jha S, Zhang L. 177.  et al. 2011. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12:408–15 [Google Scholar]
  178. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. 178.  2010. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 11:136–40 [Google Scholar]
  179. Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM. 179.  et al. 2010. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat. Immunol. 11:897–904 [Google Scholar]
  180. Ayres JS. 180.  2013. Inflammasome–microbiota interplay in host physiologies. Cell Host Microbe 14:491–97 [Google Scholar]
  181. Cho I, Blaser MJ. 181.  2012. The human microbiome: at the interface of health and disease. Nat. Rev. Genet. 13:260–70 [Google Scholar]
  182. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ. 182.  et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482:179–85 [Google Scholar]
  183. Marie J, Kovacs D, Pain C, Jouary T, Cota C. 183.  et al. 2014. Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br. J. Dermatol. 170:816–23 [Google Scholar]
  184. Zurawek M, Fichna M, Januszkiewicz-Lewandowska D, Gryczynska M, Fichna P, Nowak J. 184.  2010. A coding variant in NLRP1 is associated with autoimmune Addison's disease. Hum. Immunol. 71:530–34 [Google Scholar]
  185. Alkhateeb A, Jarun Y, Tashtoush R. 185.  2013. Polymorphisms in NLRP1 gene and susceptibility to autoimmune thyroid disease. Autoimmunity 46:215–21 [Google Scholar]
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The Inflammasomes and Autoinflammatory Syndromes
Annual Review of Pathology: Mechanisms of Disease 10, 395 (2015); https://doi.org/10.1146/annurev-pathol-012414-040431
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