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. T follicular helper cells and T follicular regulatory cells tightly control the production of (auto)antibodies by B cells. Understanding their phenotypes and how the function of these cells is dysregulated in rheumatic diseases will aid future therapeutic development.