title: Rapamycin regulates iTreg function through CD39 and Runx1 pathways.
abstract: It has been shown that rapamycin is able to significantly increase the expression of FoxP3 and suppress activity in induced Treg (iTreg) cells in vivo and in vitro. CD39 is a newly determined Treg marker that relates to cell suppression. Runx1, a regulator of FoxP3, controls the expression of adenosine deaminase (ADA) gene, which is found recently in the downstream of CD39 pathway in trophoblast cells. Whether rapamycin would influence CD39 pathway and regulate the expression of Runx1 remains to be determined. The addition of rapamycin to human CD4(+) naïve cells in the presence of IL-2, TGF-β promotes the expression of FoxP3. In this paper, we found that CD39 positively correlated with the FoxP3 expression in iTreg cells. Rapamycin induced iTreg cells showed a stronger CD39/Runx1 expression with the enhanced suppressive function. These data suggested that CD39 expression was involved in iTreg generation and the enhanced suppressive ability of rapamycin induced Treg was partly due to Runx1 pathway. We conclude that rapamycin favors CD39/Runx1 expression in human iTreg and provides a novel insight into the mechanisms of iTreg generation enhanced by rapamycin.
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jirong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qian
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center of Jiangning Hospital and Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D001081:Apyrase / Q000235:genetics* / Q000276:immunology; D050676:Core Binding Factor Alpha 2 Subunit / Q000819:agonists / Q000235:genetics* / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D061251:Primary Cell Culture; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D050676:Core Binding Factor Alpha 2 Subunit; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C493728:RUNX1 protein, human; D016212:Transforming Growth Factor beta; D001081:Apyrase; C067869:CD39 antigen; D020123:Sirolimus
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