The protective role of TIGIT + B cells in attenuating type 1 diabetes progression

Abstract Aims Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin‐producing pancreatic β‐cells. While T cells are well‐known critical, growing evidence shows that B cells also play a key role in T1D development. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), as an inhibitory immune checkpoint, is important in maintaining immune homeostasis and has become a therapeutic target for several autoimmune diseases. Our recent study identified a protective role of TIGIT+ regulatory T cells (Tregs) in T1D. However, the involvement of TIGIT+ B cells in T1D progression remains unclear. Materials and Methods This study investigated the expression, functional and metabolic characteristics of TIGIT+ B cells in T1D patients and non‐obese diabetic (NOD) mice using flow cytometry. The regulatory mechanisms were further elucidated through T cell–B cell co‐culture experiments. Additionally, in vivo intervention studies were conducted to explore potential therapeutic targets for T1D. Results We found that the frequency of TIGIT+ B cells was decreased and negatively correlated with disease progression in T1D. TIGIT+ B cells showed decreased co‐stimulation, activation, proliferation, pro‐inflammatory cytokine production, glucose metabolism and increased anti‐inflammatory cytokine production compared to TIGIT− B cells. Furthermore, in vitro co‐culture experiments revealed that TIGIT+ B cells suppressed the pro‐inflammatory differentiation and pathogenic functions of T cells. Importantly, the use of TIGIT‐immunoglobulin or adoptive transfer of TIGIT+ B cells both effectively prevented the disease onset and hyperglycaemia in cyclophosphamide‐accelerated NOD mice. Conclusions Our study provides a theoretical basis for targeting TIGIT+ B cells as a novel immunotherapy strategy for T1D.