title: IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis.
abstract: BACKGROUND
  In the respiratory mucosa, interleukin (IL)-33, has been shown to enhance T helper 2 (TH2)-type responses through the master regulatory gene GATA-3. IL-33 is upregulated in ulcerative colitis (UC), and the aim was to assess if IL-33 holds a similar key position in the shaping of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 (-/-) mice, dextran sodium sulfate (DSS) model) and UC.
  
  
  METHODS
  Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells were isolated from PAC IL-10 (-/-) mice and stimulated with IL-33.
  
  
  RESULTS
  The colonic IL-33 expression was significantly upregulated all forms of colitis (P < 0.01) and correlated with disease severity score and inflammation (P < 0.001), and with GATA-3 expression levels (P < 0.01); no correlation with the TH1-specific T-bet expression was observed. MesLN T cells stimulated with IL-33 had increased GATA-3 expression, and showed an IL-33 dose-dependent increase in secreted TH2-type cytokines, whereas this effect was abolished by blocking IL-33 signaling. The non-TH2-type cytokine IL-17 was upregulated by IL-33 but in a T cell receptor dependent manner, as opposed to TH2-type cytokines, which required only IL-33 stimulation.
  
  
  CONCLUSIONS
  The study demonstrates that intestinal IL-33 is capable of inducing GATA-3 in mucosal T cells, and suggests that IL-33 is a key mediator of pathological TH2 and non-TH2-type responses in intestinal inflammation. Blocking IL-33 signaling could be a feasible option in the treatment of UC.
authors.affiliation: Medical Section 54 O3, Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark, jseidelin@dadlnet.dk.
authors.forename: Jakob Benedict
authors.initials: JB
authors.lastname: Seidelin
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.forename: Peter Helding
authors.initials: PH
authors.lastname: Kvist
authors.forename: Thomas Lindebo
authors.initials: TL
authors.lastname: Holm
authors.forename: Kristine
authors.initials: K
authors.lastname: Holgersen
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells; D055815:Young Adult
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; C506536:IL33 protein, human; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D016753:Interleukin-10
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