2. Academic Validation
  3. Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjögren Syndrome

Increased GITRL Impairs the Function of Myeloid-Derived Suppressor Cells and Exacerbates Primary Sjögren Syndrome

  • J Immunol. 2019 Mar 15;202(6):1693-1703. doi: 10.4049/jimmunol.1801051.
Jie Tian 1 2,  Ke Rui 3,  Yue Hong 2,  Xiaohui Wang 4,  Fan Xiao 4,  Xiang Lin 4,  Jie Ma 2,  Hongye Guo 2,  Huaxi Xu 2,  Kongyang Ma 5,  Dong Xu 6,  Dongzhou Liu 5,  Yan Zhao 6,  Liwei Lu 7,  Shengjun Wang 8 2
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China.
  • 2 Jiangsu Key Laboratory of Laboratory Medicine, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
  • 3 Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
  • 4 Department of Pathology, Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong 999077, China.
  • 5 Department of Rheumatology and Immunology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China; and.
  • 6 Department of Rheumatology, Peking Union Medical College Hospital, Beijing 100730, China.
  • 7 Department of Pathology, Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong 999077, China; sjwjs@ujs.edu.cn liweilu@hku.hk.
  • 8 Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China; sjwjs@ujs.edu.cn liweilu@hku.hk.
PMID: 30760623 DOI: 10.4049/jimmunol.1801051
Abstract

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 Sjögren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjögren 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 Sjögren 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.

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