IL‐33 Aggravates DSS‐Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses

Abstract

Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4+T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

Wounds that heal and wounds that don’t − The role of the IL-33/ST2 pathway in tissue repair and tumorigenesis

“…Whilst mice deficient in ST2 demonstrate improved symptoms and reduced intestinal inflammation in the early stage of DSS colitis [41], a delay in the resolution of DSS dependent tissue damage in IL-33 -/-mice was observed [42]. This dichotomous role of IL-33 in acute versus chronic IBD was also demonstrated using a different model, as whilst injection of IL-33 aggravated DSS-induced acute colitis [43], it alleviated DSS-induced chronic colitis [44][45][46]. Indeed, in the study of Duan et al, utilising the TNBS model of colitis and treatment with recombinant IL-33, it was noted that IL-33…”

IL-33 and the intestine: The good, the bad, and the inflammatory

“…Moreover, inhibition of IL-33 signaling using an ST2 neutralizing antibody ameriolated DSS-induced colitis, whereas IL-33 treatment resulted in increased epithelial barrier permeability [124]. Additionally, treatment with recombinant IL-33 (rIL-33) exacerbated DSS-induced colitis via T H 2 polarization and inhibition of T H 1 immune responses [125–128]. This IL-33-mediated T H 2 immune response was corroborated in two models of experimental colitis with upregulation GATA-3 , which is necessary for T H 2 differentiation [126].…”

IL-33 Effect on Quantitative Changes of CD4+CD25highFOXP3+Regulatory T Cells in Children with Type 1 Diabetes

“…In mice model of type 2 diabetes (ob/ob) or Crohn's disease, conditions which are characterized by profound Th1 immune response, IL-33 induced Th2 cells and thus protected against inflammation [ 13 , 14 ]. However, in mice model of ulcerative colitis, whose pathophysiology is linked to Th2 cytokines, the harmful effect of IL-33 was seen, despite its ability to inhibit Th1-related cytokines in these mice [ 15 ].…”