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Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL‐4—producing T cells and regulatory T cells

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune‐mediated destruction of insulin‐producing β cells. Recent studies showed that in addition to malaria, artemisinin and its derivative, artesunate (AS), could alleviate several autoimmune diseases. However, whether AS has a role in the prevention or treatment of T1D is still unknown. Therefore, in this study we administrated AS or DMSO in the drinking water of nonobese diabetic (NOD) mice, a mouse model of T1D. We found that AS administration significantly prevented the incidence of T1D. The frequency of IL‐4—producing CD4+ single‐positive T cells and CD8+ T cells was significantly elevated, and IFN‐γ—producing T cells were reduced in the spleen and pancreatic lymph nodes. In the pancreas, the skewing to IL‐4—producing T cells was also observed. In addition, more regulatory T cells were found in the pancreas. mRNA levels of proinflammatory cytokines, including TNF‐α and IL‐6, were decreased. In addition, AS administration promoted the functional maturity of β cells in vitro. Our findings demonstrate that AS administration can prevent T1D in NOD mice mainly by reducing autoimmune T cells and increasing protective T cells. Our data constitute the first functional study of AS in T1D, which may provide a new rationale for future translational studies.—Li, Z., Shi, X., Liu, J., Shao, F., Huang, G., Zhou, Z., Zheng, P. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL‐4—producing T cells and regulatory T cells. FASEB J. 33, 8241–8248 (2019). www.fasebj.org