Lymphocytes in autoimmune-resistant mice may protect the islets through IL-10 production

Abstract

Abstract We have identified T cells and B cells in the islets of autoimmune resistant mice, yet the role of these lymphocytes is unknown. In the islets of autoimmune resistant C57BL/6 mice, local antigen receptor signaling was assessed using Nur77-GFP mice. Nur77-GFP expression was increased in islet CD8+ T cells and B cells suggesting that these lymphocyte subsets receive local antigenic stimulus. Islet T cell and B cell populations expressed the regulatory cytokine IL-10, assessed using the B6.TIGER reporter mouse. T cell populations lacked expression of the pro-inflammatory cytokine IFN-γ. These findings indicate that islet T cell populations are likely playing a regulatory role. In addition, cultured whole islets produced IL-10 protein, but not IFN-γ protein. To test the stability of the islet lymphocyte populations under inflammatory conditions, mice were exposed to metabolic stress through a diet-induced obesity (DIO) model. Obesity and type 2 diabetes (T2D) are associated with circulating inflammatory cytokines. In T2D patients, islet lymphocytes have been identified, though the function of these populations is largely unknown. C57BL/6 mice were fed a high fat diet (DIO) or a matched control diet (Control) starting at 5 weeks of age, and then analyzed at 16–25 weeks of age. The number and phenotype of lymphocytes in the islets were similar in DIO and control mice. Notably, under the conditions of obesity-associated systemic inflammation, islet lymphocytes in the DIO mice maintained IL-10 production. From these data, we propose that islet lymphocytes play a regulatory role to protect the islets from systemic inflammation through IL-10 production.