International immunopharmacology · 2022
Interleukin-36β exacerbates DSS-induce acute colitis via inhibiting Foxp3+ regulatory T cell response and increasing Th2 cell response.
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Zhu Junfeng, Xu Ying, Li Zheng, Liu Shanshan, Fu Wenda, Wei Yesheng
Аннотация
BACKGROUND: interleukin (IL)-36β is a member of the IL-36 subfamily of the IL-1 family. Usually, serum levels of IL-36β are higher in patients with inflammatory bowel disease (IBD), indicating that IL-36β has a pathophysiological role in IBD. At the time of writing, no studies were published reporting the role of IL-36β in modulating T cell-mediated immune responses in gastrointestinal inflammation. This research aimed to determine the function of IL-36β in regulating T cells in mice with colitis caused by dextran sulfate sodium (DSS).
METHODS: recombinant IL-36β (rIL-36β) was administered by intraperitoneal injection to mice with DSS-induced colitis. Clinical symptoms, colon length, and histological changes were determined. The production of cytokines was measured by ELISA. The help T (Th) cell subsets were measured by flow cytometry. The expression of mRNA of IL-36β was measured by quantitative real-time PCR.
RESULTS: there was an increased expression of IL-36 in the inflamed colonic mucosa of mice with DSS-induced acute colitis. Mice treated with recombinant IL-36β (rIL-36β) were more susceptible to DSS-induced colitis than PBS-treated mice. Moreover, spontaneous inflammatory cytokines produced by neutrophils greatly increased in the lamina propria lymphocytes (LPL) of rIL-36β-treated animals with DSS-induced colitis. Besides, rIL-36β-treatment dramatically elevated Th2 cell responses but significantly downregulated Foxp3+ regulatory T cell (Treg) responses.
CONCLUSION: these findings indicate that IL-36β enhances the pathology of DSS-induced colitis in mice by promoting Th2 responses in LPL while decreasing Foxp3+ Treg responses. Thus, we propose the regulation of the IL-36β/IL-36R signaling pathway as a potential biological treatment for IBD.
METHODS: recombinant IL-36β (rIL-36β) was administered by intraperitoneal injection to mice with DSS-induced colitis. Clinical symptoms, colon length, and histological changes were determined. The production of cytokines was measured by ELISA. The help T (Th) cell subsets were measured by flow cytometry. The expression of mRNA of IL-36β was measured by quantitative real-time PCR.
RESULTS: there was an increased expression of IL-36 in the inflamed colonic mucosa of mice with DSS-induced acute colitis. Mice treated with recombinant IL-36β (rIL-36β) were more susceptible to DSS-induced colitis than PBS-treated mice. Moreover, spontaneous inflammatory cytokines produced by neutrophils greatly increased in the lamina propria lymphocytes (LPL) of rIL-36β-treated animals with DSS-induced colitis. Besides, rIL-36β-treatment dramatically elevated Th2 cell responses but significantly downregulated Foxp3+ regulatory T cell (Treg) responses.
CONCLUSION: these findings indicate that IL-36β enhances the pathology of DSS-induced colitis in mice by promoting Th2 responses in LPL while decreasing Foxp3+ Treg responses. Thus, we propose the regulation of the IL-36β/IL-36R signaling pathway as a potential biological treatment for IBD.