Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjogren Syndrome
Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjogren Syndrome
复制标题
GITRL 增加会损害骨髓源性抑制细胞的功能并加剧原发性干燥综合征
DOI：
10.4049/jimmunol.1801051
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发表时间：
2019-03-15
影响因子：
4.4
通讯作者：
Wang, Shengjun
中科院分区：
文献类型：
--
作者：
Tian, Jie;Rui, Ke;Wang, Shengjun
Although the expansion of myeloid-derived suppressor cells (MDSCs) has been reported in autoimmune disorders, it is largely unclear how MDSCs contribute to the development of primary Sjogren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjogren syndrome (ESS). The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased along ESS progression, whereas the increased GITRL was found to attenuate the immunosuppressive function of MDSCs. Moreover, blocking GITR signal in MDSCs significantly restored their immunosuppressive function and alleviated ESS progression in mice. In pSS patients, expanded MDSCs were found to express low levels of arginase. Significantly increased serum GITRL levels were closely correlated with patients with higher Sjogren syndrome disease activity index. Furthermore, treatment with recombinant GITRL markedly reduced the immunosuppressive function of human MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive function of MDSCs, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.
