Journal of Inflammation Research (Jul 2022)
Inflammatory Cytokine-Neutralizing Antibody Treatment Prevented Increases in Follicular Helper T Cells and Follicular Regulatory T Cells in a Mouse Model of Arthritis
Abstract
Xingyue Zeng,1,* Songsong Lu,1,* Meng Li,1 Mohan Zheng,2 Tianci Liu,1 Rui Kang,1 Lijuan Xu,3 Qinzhu Xu,1 Ying Song,1 Chen Liu1 1Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Liu, Department of Clinical Laboratory, Peking University People’s Hospital, 11# Xizhimen South Street, Beijing, 100044, People’s Republic of China, Tel +86 10 88326203, Fax +86 10 88326300, Email [email protected]: Follicular T helper (TFH) and follicular regulatory T (TFR) cells play important roles in humoral immunity. Nevertheless, their significance in rheumatoid arthritis (RA) pathogenesis has not been fully elucidated. As an important treatment strategy, the effect of inflammatory factor-neutralizing antibodies on TFH and TFR in RA remains unclear.Methods: We used the collagen-induced arthritis (CIA) mouse model to illustrate the quantity and functional changes in TFH and TFR cells. The changes of plasmablast, TFH and TFR cells in the spleen and peripheral blood of CIA mice were analyzed by flow cytometry. The levels of TFH and TFR and their functional subsets in the spleen after anti-inflammatory antibody treatment were analyzed and compared. The functional changes of TFH and TFR in CIA mice before and after treatment were detected by in vitro culture experiments.Results: Plasmablast levels were increased in CIA spleen and peripheral blood and both TFH and TFR cell levels were upregulated. TFH and TFR cells were decreased significantly after the anti-inflammatory antibody treatment. TIGIT+ and TIGIT+CD226− TFH cells in CIA mouse spleen were elevated and PD-1 and ICOS expression on spleen TFH and TFR cells was increased. Both the ability of TFH cells to secrete IL-21 and aid B cells and the ability of TFR cells to secrete IL-10 and inhibit TFH cells were enhanced in the CIA mice. After antibody treatment, the cell subsets and functions were recovered.Conclusion: Germinal center TFH and TFR cells were increased and their functions were enhanced. With inflammatory factor-neutralizing antibody treatment, TFH and TFR subsets and their functions returned to normal. These findings provide important information on the dynamics of humoral immune-related cell subsets in RA and the effects of treatment on them.Keywords: TFH, TFR, collagen-induced arthritis, rheumatoid arthritis, inflammatory cytokines
