T follicular helper cells and T follicular regulatory cells in rheumatic diseases

As a hallmark of autoimmune rheumatic diseases, autoantibodies have been used in diagnosis for decades. However, the immunological mechanism underlying their generation has only become clear following the identification of T follicular helper (TFH) cells and T follicular regulatory (TFR) cells. TFH cells are instrumental in supporting antibody affinity maturation in germinal centre reactions and humoral memory formation, whereas TFR cells suppress TFH cell-mediated antibody responses. Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of TFH cells that can be hyperactive, and also potentially have altered numbers of TFR cells with reduced function, suggesting a conceivable dysregulation in the balance between TFH cells and TFR cells in these diseases. Therefore, by identifying the molecular mechanisms underlying the development and function of these cell populations, new opportunities have emerged to develop novel therapeutic targets. An increased knowledge of TFH cells and TFR cells has inspired, and hopefully will inspire more, approaches to reinstate the balance of these cells in the prevention and treatment of rheumatic diseases.The work of the authors was funded by grants from the National Key Research and Development Program of China (2017YFC0909003 to D.Y.), the National Natural Science Foundation of China (31600708 to J.D. and 81429003 to D.Y.), the Australian National Health and Medical Research Council (GNT1147769 to D.Y.), the Shandong Provincial Natural Science Foundation, China (ZR2016YL013 to D.Y. and ZR2015YL005 to D.Y. and Y.W.) and the Priority Research Program of the Shandong Academy of Sciences (to D.Y. and Y.W.). D.Y. is supported by the Bellberry-Viertel Senior Medical Research Fellowship, Innovative Research Team of High-Level Local Universities in Shanghai, and the Taishan Scholars Program of Shandong Province, China