![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Background
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.
Abbreviations
ANOVA, Analysis of variance; ARRIVE, Animal Research: Reporting of In Vivo Experiments guidelines; Bcl-6, B cell lymphoma 6; Blimp1, B lymphocyte-induced maturation protein-1; CIA, collagen-induced arthritis; CII, type II collagen; FCA, Freund’s complete adjuvant; FIA, Freund’s incomplete adjuvant; FoxP3, forkhead box P3; GITR, glucocorticoid-induced TNF receptor; ICOS, inducible costimulator; IFN, interferon; IL, interleukin; PD-1, programmed cell death 1; PD-L1, programmed death ligand 1; PMA, phorbol 12-myristate 12-acetate; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TFH, follicular helper T cells; TFR, follicular regulatory T cells; TIGIT, T cell Ig and ITIM domain; TNF, tumor necrosis factor; Treg, regulatory T cells.
Data Sharing Statement
All supporting data in this study are available from the corresponding author on reasonable request.
Ethics Approval Statement for Animal Studies
All mice received humane care and the research protocol was approved by the ethical board of Peking University People’s Hospital.
Acknowledgments
We thank the Department of Animal Unit of Peking University People’s Hospital for their service.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.