title: The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft Rejection.
abstract: BACKGROUND
  Lung transplantation is the only definitive therapy for many forms of end-stage lung disease. Studies have demonstrated the critical role of interleukin (IL)-17 in the development of lung rejection. Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance.
  
  
  METHODS
  We established mouse orthotopic lung transplantation models to investigate the importance of IL-17 and IL-17-producing cell types in acute lung allograft rejection and the efficacy of the adoptive transfer of induced Tregs (iTregs) in attenuating pathologic lesions of lung allografts.
  
  
  RESULTS
  We found that the IL-17 produced by Th17 cells and γδ T cells might make the primary contributions to the progression of acute lung allograft rejection. Interleukin-17 deficiency decreased lung allograft lesions. Exogenous iTregs maintained their FoxP3 expression levels in lung allograft recipients. Induced Tregs therapy downregulated the expressions of Th17 and IL-17 γδ T cells and increased IL-10 production in the mouse orthotopic lung transplantation models. Moreover, the adoptive transfer of iTregs prolonged the survivals of the lung allografts and attenuated the progression of acute rejection.
  
  
  CONCLUSIONS
  These data suggested that the adoptive transfer of iTregs could suppress the Th17 cells and IL-17 γδ cells of the recipients, decrease the expression of IL-17, and attenuate the pathology of acute lung allograft rejection. Exogenous iTregs upregulated immunosuppressive factors, such as IL-10 and suppressed IL-17-producing cells, which was one of the pathways to play a role in protecting lung allografts.
authors: 1 Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 2 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Wenyong
authors: W
authors: Zhou
authors: Xiaohui
authors: X
authors: Zhou
authors: Saren
authors: S
authors: Gaowa
authors: Qingshu
authors: Q
authors: Meng
authors: Zhenzhen
authors: Z
authors: Zhan
authors: Jie
authors: J
authors: Liu
authors: Jing
authors: J
authors: Li
authors: Huimin
authors: H
authors: Fan
authors: Zhongmin
authors: Z
authors: Liu
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D064591:Allografts; D000818:Animals; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D023001:Transplantation Tolerance; D055114:X-Ray Microtomography
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta