Follicular helper T cells in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by the dysfunction of immune system and consequently the destruction of insulin‐producing β cells. In past decades, numerous studies have uncovered that CD4+ T cell subsets are critical in the pathogenesis of T1D, manifesting that type 1 T helper (Th1) and Th17 cells are pathogenic, while regulatory T (Treg) cells and Th2 cells are protective. More recently, the pathogenic role of another subset, follicular helper T (Tfh) cells that essentially regulate germinal center (GC) formation and humoral responses, has also been demonstrated in T1D and many other autoimmune diseases. In this review, we summarize the evidence for the aberrant differentiation and function of Tfh cells in T1D, and also discuss the underlying mechanisms. A better understanding on the pathogenic role of Tfh cells in T1D will inspire the design of potential therapeutic strategies to target this subset in the future.

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

“…Moreover, the phenotypes of Tfh cells are associated with different stages of immune responses ( 30 , 31 ). In secondary lymphoid organs, naïve CD4 + T cells are differentiated into Tfh cells with the upregulation of CXCR5 and downregulation of CC-chemokine receptor 7 (CCR7), which are mediated by antigen-specific conventional dendritic cells (DCs) or monocyte-derived DCs ( 28 , 32 , 33 ). The increased CXCR5 and decreased CCR7contribute to the migration of Tfh cells toward CXC-chemokine ligand 13 (CXCL13)-enriched B lymphoid follicles in the germinal center (GC) ( 28 , 34 ).…”

Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus

“…Since autoreactive T cell clones have been demonstrated to expand during homeostatic proliferation following induction, the concomitant assessment of T cell and autoantibody levels may further elaborate the mechanistic involvement of GADA, IA-2A, and ZnT8A in disease pathogenesis. Given the ability of certain immunosuppressive regimens to affect the development of auto- and allo-reactivity, exploring the dynamics of T and B cell responses to islet transplantation in the context of different pharmacologic regimens (Reparixin versus placebo versus anti-TNF agents; anti-thymocyte globulin versus basiliximab; rapamycin versus tacrolimus) could contribute to characterizing the effects of specific drugs on the immune system and their safety and efficacy for the prevention of islet graft failure [ 22 , 23 ]. We anticipate that the identification of reliable markers of islet graft failure will depend upon the broad and combined characterization of T and B cell phenotypes, and that these data could lead to improved therapeutic approaches.…”

Clinical Translational Potentials of Stem Cell-Derived Extracellular Vesicles in Type 1 Diabetes

“…CD4+ T cells can give rise to different functional subsets in response to different signals, offering to "help" effector immune cells in their immune response (41). Increasing evidence has demonstrated that multiple CD4+ T cells are involved in the development of insulitis, including T-helpers type 1, 2, and 17 (Th1, Th2, and Th17), regulatory T cells (Treg), and follicular B helper T cells (Tfh) (42)(43)(44). Studies have revealed an altered balance between Th1/Th17 and Th2 immune responses leading to T1D (45,46).…”