中华临床免疫和变态反应杂志2018，Vol.12Issue(2)：141-150,10.DOI:10.3969∕j.issn.1673-8705.2018.02.002
胶原诱导关节炎模型中髓系来源抑制细胞通过白细胞介素-1β促进Th17细胞分化的作用
Myeloid-derived suppressor cells depend on IL-1βpromote Th17 cell differentiation in autoimmune arthritis
摘要
Abstract
Objective To investigate the role and mechanism of myeloid-derived suppressor cells ( MD-SCs) on Th17 cell differentiation by using collagen induced arthritis (CIA) model. To elucidate the pathogenesis of autoimmune arthritis and find new therapeutic targets. Methods SPF male DBA1/J mice were randomly divided into CIA group ( n=10) and control group ( n=10) . An autoimmune arthritis mouse model was prepared by CIA method. The proportion of MDSCs and Th17 cells were examined in each group by flow cytometry. The levels of plasma IL-1β, IL-10, and IL-17A were detected by ELISA. The relative expression levels of factor-related to Th17 differentiation, such as STAT3 mRNA, retinoic acid associated orphine receptor ( ROR) αmRNA and RORγt mRNA, were detected by real-time fluorescence quantitative PCR. The effects of MDSCs on the differentiation of Th17 cells in CIA mice were assessed by coculture of MDSCs with mouse naive CD4+T cells under the condition of Th17 cell differentiation ( IL-6+TGF-β) . It was also observed by adding IL-1βmAb or IL-1ra when coculturing MDSCs with CD4+T cells. Results Compared with the control group, the proportion of MDSCs and plasma IL-17 level were significantly elevated [ MDSCs: ( 20. 1 ± 2. 6 )% vs. ( 2. 6 ± 1. 17)%;IL-17: (1. 3±0. 2)% vs. (0. 3±0. 1)%], the levels of IL-1βand the relative expression of RORγt mRNA were significantly increased and IL-10 was lowed ( P<0. 01) . The proportion of MDSCs was positively correlated to the proportion of Th17 cells in CIA mice. MDSCs inhibited the proliferation of CD4+T cells and the secretion of gamma interferon ( IFN-γ) in CIA. In contrast, MDSCs promoted Th17 cells differentiation in vitro, followed by significant increase of IL-17A, IL-1β, and upregulation of STAT3 and RORγt. The effect of MDSCs in differentiation of Th17 cells was down-regulated when IL-1β pathway was blocked. Conclusions MDSCs play a role in promoting inflammation by driving Th17 cell differentiation in autoimmune arthritis, which depends on IL-1β pathway. MDSCs may be a potential target in treatment of autoimmune arthritis.关键词
髓系来源抑制细胞/自身免疫病/胶原诱导关节炎/白细胞介素-1β/辅助T细胞17Key words
Myeloid-derived suppressor cells/Autoimmune disease/Collagen induced arthritis/Inter-leukin-1β/Th17 cells引用本文复制引用
程苏云,陈香元,李洪伟,谢颖,李丰,曾华松..胶原诱导关节炎模型中髓系来源抑制细胞通过白细胞介素-1β促进Th17细胞分化的作用[J].中华临床免疫和变态反应杂志,2018,12(2):141-150,10.基金项目
广东省自然基金(2017A030313557) （2017A030313557）
广州市科技计划项目(2016070103160) （2016070103160）
广东省科技厅资助项目(2014A020212010) Guangdong Natural Foundation(2017A030313557) （2014A020212010）
Guangzhou Science and Technology Project(2016070103160) （2016070103160）
Guangdong Provincial Science and Technology Foundation(2014A020212010) （2014A020212010）
