Chinese medicine Ginseng and Astragalus granules ameliorate autoimmune diabetes by upregulating both CD4+FoxP3+ and CD8+CD122+PD1+ regulatory T cells.

// Yeshu Wang 1, * , Qingfeng Xie 2, * , Chun-Ling Liang 3, * , Qiaohuang Zeng 1 and Zhenhua Dai 3 1 Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China 2 Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China 3 Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China * These authors have contributed equally to this work Correspondence to: Zhenhua Dai, email: zdai2009@outlook.com Keywords: autoimmunity, type 1 diabetes, regulatory T cells, Chinese medicine Abbreviations: CsA, cyclosporine; GAG, ginseng and astragalus granule; T1DM, type 1 diabetes mellitus; Treg, regulatory T cell Received: March 21, 2017      Accepted: April 27, 2017      Published: June 27, 2017 ABSTRACT Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China. Here we found that GAG ameliorated T1DM in autoimmune NOD mice by increasing the level of insulin and reducing the level of blood glucose. Treatments with both GAG and CsA further decreased the blood glucose level. Moreover, GAG increased both CD4+FoxP3+ and CD8+CD122+PD-1+ Treg numbers in both spleens and lymph nodes of NOD mice. In particular, GAG could reverse a decline in CD4+FoxP3+ Tregs resulted from CsA treatments. The percentage of effector/memory CD8+ T cells (CD44 high CD62L low ) was significantly reduced by GAG, especially in the presence of low-doses of CsA. Histopathology also showed that GAG attenuated cellular infiltration and lowered CD3+ T cell numbers around and in islets. Thus, we demonstrated that GAG ameliorated autoimmune T1DM by upregulating both CD4+FoxP3+ and CD8+CD122+PD-1+ Tregs while GAG synergized with CsA to further suppress autoimmunity and T1DM by reversing the decline in CD4+FoxP3+ Tregs resulted from CsA treatments. This study may have important clinical implications for the treatment of T1DM using traditional Chinese medicine.