Induction of CD4+CD25+Foxp3+ regulatory T cell response by glatiramer acetate in type 1 diabetes.
Glatiramer acetate (GA) is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft rejection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclophosphamide (CY)-potentiated non-obese diabetic (CY-NOD) mice. Treatment with GA significantly reduced the diabetic rate in the mice and ameliorated insulitis, which coincided with increased CD4+CD25+Foxp3+ T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 (IL-4) both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was mediated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4+CD25+ regulatory T cells (Tregs). This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg's function in GA treatment.
Cui
Guoliang
G
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, 319 Yue Yang Road, Shanghai 200031, China.
Zhang
Yuebo
Y
Gong
Zhenwei
Z
Zhang
Jingwu Z
JZ
Zang
Ying Qin
YQ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000068717:Glatiramer Acetate; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007004:Hypoglycemic Agents; D010455:Peptides; D015847:Interleukin-4; D000068717:Glatiramer Acetate