title: Antagonistic effect of the inflammasome on thymic stromal lymphopoietin expression in the skin.
abstract: BACKGROUND
  Innate immune sensors control key cytokines that regulate T-cell priming and T-cell fate. This is particularly evident in allergic reactions, which represent ideal systems to study the interplay of innate and adaptive immunity. In patients with contact dermatitis, inflammasome-mediated IL-1 activation is responsible for a TH1 immune response. Surprisingly, the IL-1 signaling pathway was also proposed to control the activation of thymic stromal lymphopoietin (TSLP), a cytokine implicated in development of the T(H)2 response in patients with atopic dermatitis (AD) and asthma.
  
  
  OBJECTIVE
  We sought to assess the effect of the inflammasome on TSLP expression levels and the development of AD.
  
  
  METHODS
  We studied the effect of the inflammasome activator 2,4-dinitrofluorobenzene, and IL-1β on TSLP mRNA expression levels in mouse and human cell lines (in vitro assays), as well as in live mice and on human skin transplants. We also assessed the effect of 2,4-dinitrofluorobenzene on TSLP and the TH2 response in mice in which the inflammasome and IL-1 signaling pathways were blocked, either genetically or pharmacologically, in 2 models of AD.
  
  
  RESULTS
  We provide in vitro and in vivo evidence that inflammasome activation has an inhibitory role on TSLP mRNA expression and T(H)2 cell fate in the skin. We also show that solvents influence the activation of TSLP and IL-1β and direct the T-cell fate to a given hapten.
  
  
  CONCLUSIONS
  Our observations strongly suggest that the TH1 versus TH2 cell fate decision is regulated at multiple levels and starts with innate immune events occurring within peripheral epithelial tissues.
authors: Departments of Dermatology and Pathology/Immunology, Geneva University Medical School, Geneva, Switzerland.
authors: Sonia
authors: S
authors: Schuepbach-Mallepell
authors: Virginie
authors: V
authors: Philippe
authors: Marie-Charlotte
authors: MC
authors: Brüggen
authors: Hideki
authors: H
authors: Watanabe
authors: Stéphanie
authors: S
authors: Roques
authors: Christine
authors: C
authors: Baldeschi
authors: Olivier
authors: O
authors: Gaide
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D004139:Dinitrofluorobenzene; D000094632:Thymic Stromal Lymphopoietin
keywords: 2,4-Dinitrochlorobenzene; 2,4-Dinitrofluorobenzene; 2,4-Dinitrothiocyanobenzene; 9-Cis-retinoic acid; 9-cis-RA; AD; ASC; Acetone dibutyl phthalate (1:1 vol); Acetone olive oil (3:1 vol); Apoptosis-associated speck-like protein containing a caspase recruitment domain; Atopic dermatitis; Atopy; DBP; DNCB; DNFB; DNTB; Dibutyl phthalate; FITC; Fluorescein isothiocyanate; IL-1; IL-1 receptor; IL-1 receptor antagonist; IL-1R; IL-Ra; NACHT-, LRR-, and PYD-containing protein; NALP; NOD; Nucleotide-binding oligomerization domain; Quantitative PCR; T(H)1; T(H)2; TSLP; Thymic stromal lymphopoietin; aDBP; aOO; asthma; atopic dermatitis; inflammasome; qPCR; thymic stromal lymphopoietin