title: Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells.
abstract: Recent studies have demonstrated that complement contributes to the development of autoimmune diabetes. However, the mechanisms remain unknown. Herein, using a model of streptozotocin (STZ)-induced diabetes, we found the presence of immune tolerance to self islet in complement C3-deficient mice after STZ. Higher number of CD4+CD25+ regulatory T cells (Tregs) with characteristics of expressing Foxp3 was observed in C3-/- mice. These C3-/- Tregs exhibited enhanced suppressive capacity to effector cell proliferation. The central role of Tregs was further evidenced by that depleting these cells using anti-CD25 antibody dramatically abrogated the preventive effects of C3 deficiency on STZ-induced diabetes. Importantly, transforming growth factor-β (TGF-β) was a key factor for Treg-mediated immune suppression as blocking TGF-β activity reversed suppressive capacity of Tregs in vitro and diabetes-resistant effects of C3 deficiency in vivo. These findings suggest that resistance to overt diabetes in STZ-treated C3-/- mice involves a population of Tregs in TGF-β-dependent manner.
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, PR China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Gao
authors.forename: Huanhai
authors.initials: H
authors.lastname: Liu
authors.forename: Guoshan
authors.initials: G
authors.lastname: Ding
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Fu
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Ni
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D003176:Complement C3; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta