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

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.

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.

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.

Our study provides a theoretical basis for targeting TIGIT+ B cells as a novel immunotherapy strategy for T1D.