AUTHOR=Wei Xundong , Zhang Jianhua , Zhou Xuyu TITLE=Ex-TFRs: A Missing Piece of the SLE Puzzle? JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.662305 DOI=10.3389/fimmu.2021.662305 ISSN=1664-3224 ABSTRACT=

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease involving the production of a wide range of autoantibodies and complement activation. The production of these high-affinity autoantibodies requires T cell/B cell collaboration as well as germinal center (GC) formation. T follicular regulatory cells (TFRs) are functional specialized T regulatory cells (Tregs) that safeguard against both self-reactive T and B cells. However, recent evidence suggests that TFRs are not always stable and can lose Foxp3 expression to become pathogenic “ex-TFRs” that gain potent effector functions. In this review, we summarize the literature on intrinsic and extrinsic mechanisms of regulation of TFR stability and discuss the potential role of TFR reprogramming in autoantibody production and SLE pathogenesis.