Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, China.
Office of Drug Clinical Trials, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, China.
Int Immunopharmacol. 2022 Jul;108:108762. doi: 10.1016/j.intimp.2022.108762. Epub 2022 Apr 15.
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).
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.
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.
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.
白细胞介素（IL）-36β是白细胞介素 1 家族中 IL-36 亚家族的成员。通常，炎症性肠病（IBD）患者的血清 IL-36β 水平较高，表明 IL-36β 在 IBD 中具有病理生理作用。在撰写本文时，尚无研究报道 IL-36β在调节胃肠道炎症中的 T 细胞介导的免疫反应中的作用。本研究旨在确定 IL-36β在调节葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠中 T 细胞中的功能。
通过腹腔注射重组 IL-36β（rIL-36β）对 DSS 诱导的结肠炎小鼠进行治疗。通过酶联免疫吸附试验（ELISA）测定细胞因子的产生。通过流式细胞术测定辅助性 T（Th）细胞亚群。通过实时定量 PCR 测定 IL-36β 的 mRNA 表达。
DSS 诱导的急性结肠炎小鼠结肠黏膜中 IL-36 的表达增加。与 PBS 处理的小鼠相比，用重组 IL-36β（rIL-36β）处理的小鼠对 DSS 诱导的结肠炎更为敏感。此外，rIL-36β 处理的动物的固有层淋巴细胞（LPL）中自发产生的炎性细胞因子大大增加。此外，rIL-36β 处理可显著提高 Th2 细胞反应，但显著降低 Foxp3 调节性 T 细胞（Treg）反应。
这些发现表明，IL-36β 通过促进 LPL 中的 Th2 反应而降低 Foxp3 Treg 反应，从而增强 DSS 诱导的结肠炎小鼠的病理学。因此，我们提出调节 IL-36β/IL-36R 信号通路作为治疗 IBD 的潜在生物学方法。
