BTNL2-Ig Protein Attenuates Type 1 Diabetes in Non-Obese Diabetic (NOD) Mice.

Abstract

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which insulin-producing β-cells are destroyed. Although butyrophilin-like 2 (BTNL2) has been shown to be a negative T cell regulator in vitro, its ability to inhibit T cell responses in vivo has not been determined. In this study, the effect of a recombinant BTNL2-IgG2a Fc (rBTNL2-Ig) fusion protein on T1D development in vivo is determined. It is shown here that in vivo administration of rBTNL2-Ig ameliorates T1D in non-obese diabetic (NOD) mice. This is associated with the ability of rBTNL2-Ig to inhibit the proliferation, activation, and inflammatory cytokine production from autoreactive T cells in vivo. In addition, rBTNL2-Ig treatment increases the generation of regulatory T cells. The results suggest that targeting the BTNL2 pathway has the potential to be used in the prevention and treatment of patients with T1D.