Shuai Xu, Wei-min Li, Tong Ya-lin, Dong Ning, Sheng Zhi-yong, Yao Yong-ming
Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
Department of Hepatobiliary Surgery, the 309th Hospital of Chinese PLA, Beijing 100091, China.
Sci Rep. 2015 Sep 28;5:14478. doi: 10.1038/srep14478.
Interleukin-37 (IL-37) possesses the function of down-regulate systemic and local inflammation. It is unknown whether IL-37 is expressed in human regulatory T cells (Tregs) and its role in modulating the immune response of Tregs. In the present study, cell surface molecules and secretory cytokines were analyzed in order to determine the function of IL-37 in regulating inhibitory effect of human CD4(+)CD25(+)Tregs. Meanwhile, the effects of IL-37 on T cell differentiation and proliferation as co-culture of CD4(+)CD25(+)Treg/CD4(+)CD25(-)T cell were also investigated. It was showed that IL-37 was expressed in cytoplasm of CD4(+)CD25(+)Tregs, and the levels of IL-37 were gradually elevated with the enhanced activity of CD4(+)CD25(+)Tregs. Secretory cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10, and expressions of cell surface molecules, including forkhead/winged helix transcription factor p3 (FOXP3) and cytotoxic T-lymphocyte associated antigen (CTLA)-4, were significantly decreased when IL-37 gene was silenced by siRNA. Furthermore, down-regulation of IL-37 expression in human CD4(+)CD25(+)Tregs obviously promoted proliferation of co-cultured T cell and differentiation, together with observably enhancement of IL-2 formation. These results demonstrated that IL-37 might manifest as a critical protein involving in immunosuppression of human CD4(+)CD25(+)Tregs.
白细胞介素-37（IL-37）具有下调全身和局部炎症的功能。目前尚不清楚IL-37是否在人类调节性T细胞（Tregs）中表达及其在调节Tregs免疫反应中的作用。在本研究中，分析了细胞表面分子和分泌的细胞因子，以确定IL-37在调节人类CD4(+)CD25(+)Tregs抑制作用中的功能。同时，还研究了IL-37对T细胞分化和增殖的影响，即作为CD4(+)CD25(+)Treg/CD4(+)CD25(-)T细胞共培养物的影响。结果表明，IL-37在CD4(+)CD25(+)Tregs的细胞质中表达，并且随着CD4(+)CD25(+)Tregs活性的增强，IL-37的水平逐渐升高。当用小干扰RNA（siRNA）使IL-37基因沉默时，分泌的细胞因子如转化生长因子（TGF）-β和白细胞介素（IL）-10以及细胞表面分子的表达，包括叉头/翼状螺旋转录因子p3（FOXP3）和细胞毒性T淋巴细胞相关抗原（CTLA）-4，均显著降低。此外，人类CD4(+)CD25(+)Tregs中IL-37表达的下调明显促进了共培养T细胞的增殖和分化，同时显著增强了IL-2的形成。这些结果表明，IL-37可能是参与人类CD4(+)CD25(+)Tregs免疫抑制的关键蛋白。
