title: IL-25 promotes the function of CD4+CD25+ T regulatory cells and prolongs skin-graft survival in murine models.
abstract: Interleukin (IL)-25, also known as IL-17E, belongs to the IL-17 family of cytokines. Unlike other IL-17 family members, IL-25 promotes Th2-type immune responses, stimulating IL-4, IL-5, and IL-13 production. Here, we employed murine models of skin graft to explore the role of IL-25 in suppression of graft rejection. We found that IL-25 expression is increased during allograft rejection, and allograft rejection was enhanced in IL-25 KO mice. IL-25 KO was associated with down-regulation of Foxp3 expression in CD4+ T cells. Further, while adoptive transfer of WT regulatory T cells (Tregs) protected against allograft rejection, adoptive transfer of IL-25 deficient Tregs failed to protect against allograft rejection. Exogenous IL-25 restored Foxp3 expression and Treg function in vitro. Moreover, IL-25 promoted phosphorylation of NFAT2. Thus, IL-25 may enhance Treg function by up-regulating NFAT2 phosphorylation. Our findings suggest that IL-25 can sustain Foxp3 expression, enhance the suppressive function of Tregs, and prolong skin-graft survival.
authors: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, China.
authors: Jiayou
authors: J
authors: Tang
authors: Research Center for Translational Medicine, Tongji University School of Medicine, China; Shanghai Heart Failure Research Center, Tongji University School of Medicine, China.
authors: Xiaohui
authors: X
authors: Zhou
authors: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, China.
authors: Jie
authors: J
authors: Liu
authors: Research Center for Translational Medicine, Tongji University School of Medicine, China; Shanghai Heart Failure Research Center, Tongji University School of Medicine, China.
authors: Qingshu
authors: Q
authors: Meng
authors: Department of Pathology, Shanghai East Hospital, Tongji University School of Medicine, China.
authors: Yang
authors: Y
authors: Han
authors: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, China.
authors: Zhulin
authors: Z
authors: Wang
authors: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, China; Research Center for Translational Medicine, Tongji University School of Medicine, China; Shanghai Heart Failure Research Center, Tongji University School of Medicine, China. Electronic address: frankfan@tongji.edu.cn.
authors: Huimin
authors: H
authors: Fan
authors: Department of Cardiovascular and Thoracic Surgery, Tongji University School of Medicine, China; Research Center for Translational Medicine, Tongji University School of Medicine, China; Shanghai Heart Failure Research Center, Tongji University School of Medicine, China. Electronic address: zhongmin_liu@sina.com.
authors: Zhongmin
authors: Z
authors: Liu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000276:immunology; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007378:Interleukins; C442281:Mydgf protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse
keywords: Interleukin-25; NFAT2; Regulatory T cells; Skin transplantation