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 (T_FH) cells and T follicular regulatory (T_FR) cells. T_FH cells are instrumental in supporting antibody affinity maturation in germinal centre reactions and humoral memory formation, whereas T_FR cells suppress T_FH cell-mediated antibody responses. Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of T_FH cells that can be hyperactive, and also potentially have altered numbers of T_FR cells with reduced function, suggesting a conceivable dysregulation in the balance between T_FH cells and T_FR 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 T_FH cells and T_FR cells has inspired, and hopefully will inspire more, approaches to reinstate the balance of these cells in the prevention and treatment of rheumatic diseases.

Nature Reviews Rheumatologyvolume 15, pages475–490(2019)