T-Follicular Regulatory Cells: Potential Therapeutic Targets in Rheumatoid Arthritis.

Tingting Ding,Xiaofeng Li,Caihong Wang,Xiangcong Zhao,Hongqing Niu,Chong Gao

doi:10.3389/fimmu.2019.02709

Abstract

Rheumatoid arthritis (RA) is an incurable aggressive chronic inflammatory joint disease with a worldwide prevalence. High levels of autoantibodies and chronic inflammation may be involved in the pathology. Notably, T follicular regulatory (Tfr) cells are critical mediators of T follicular helper (Tfh) cell generation and antibody production in the germinal center (GC) reaction. Changes in the number and function of Tfr cells may lead to dysregulation of the GC reaction and the production of aberrant autoantibodies. Regulation of the function and number of Tfr cells could be an effective strategy for precisely controlling antibody production, reestablishing immune homeostasis, and thereby improving the outcome of RA. This review summarizes advances in our understanding of the biology and functions of Tfr cells. The involvement of Tfr cells and other immune cell subsets in RA is also discussed. Furthermore, we highlight the potential therapeutic targets related to Tfr cells and restoring the Tfr/Tfh balance via cytokines, microRNAs, the mammalian target of rapamycin (mTOR) signaling pathway, and the gut microbiota, which will facilitate further research on RA and other immune-mediated diseases.

Highlights

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving damage to the joint synovium and irreversible disability [1]
programmed cell death 1 (PD-1) suppresses the generation of long-lived plasma cells through reducing T follicular helper (Tfh) cell-associated cytokine production [53], blockade of PD-1 signaling pathway leads to enhanced humoral immunity [54, 55]
IL-2 represses B-cell lymphoma 6 (Bcl-6) expression via the STAT5 pathway, which precludes the differentiation of Tfh cells and so controls the germinal center (GC) reaction [133, 134]

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving damage to the joint synovium and irreversible disability [1]. T follicular regulatory (Tfr) cells, a subpopulation of regulatory T cells (Tregs), have potential for immune regulation within GCs, inhibiting the GC reaction and interacting with Tfh and/or B cells to suppress production of high-affinity antibodies [14,15,16]. PD-1 suppresses the generation of long-lived plasma cells through reducing Tfh cell-associated cytokine production [53], blockade of PD-1 signaling pathway leads to enhanced humoral immunity [54, 55].

Results

Conclusion