Blockade of Glucocorticoid-Induced Tumor Necrosis Factor-Receptor-Related Protein Signaling Ameliorates Murine Collagen-Induced Arthritis by Modulating Follicular Helper T Cells.
Recent studies have shown that glucocorticoid-induced tumor necrosis factor-receptor-related protein (GITR) and its ligand (GITRL) are critically involved in the pathogenesis of autoimmune arthritis, but the role of GITRL/GITR signaling in modulating CD4(+) follicular helper T (Tfh) cell response during autoimmune arthritis remains largely unclear. We showed that splenic Tfh cells from mice with collagen-induced arthritis expressed higher levels of GITR compared with non-Tfh cells. In vitro, GITRL treatment markedly enhanced the percentage and number of Tfh cells. The administration of GITR fused to fragment crystallizable of IgG protein in mice with collagen-induced arthritis suppressed the Tfh cell response, resulting in ameliorated disease severity, and reduced production of autoantibody and the number of autoantibody-secreting cells in both the spleen and bone marrow. Together, these results indicate that blockade of GITR signaling can ameliorate arthritis progression mainly by modulating the Tfh cell response.
Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China; Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Jie
J
Ma
Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China; Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Dingqi
D
Feng
Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Yancai
Y
Wei
Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Jie
J
Tian
Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
Xinyi
X
Tang
Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Ke
K
Rui
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Liwei
L
Lu
Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Huaxi
H
Xu
Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China; Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China. Electronic address: sjwjs@ujs.edu.cn.
Shengjun
S
Wang
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism*
D053450:Glucocorticoid-Induced TNFR-Related Protein; C106544:Tnfrsf18 protein, mouse; C478966:Tnfsf18 protein, mouse; D048069:Tumor Necrosis Factors