title: Adoptively transferred donor IL-17-producing CD4+T cells augment, but IL-17 alleviates, acute graft-versus-host disease.
abstract: The role of IL-17 and IL-17-producing CD4+T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4+T cells exacerbated acute GVHD compared with IL-17-/-CD4+T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4+T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs. Furthermore, IL-17 reduced the infiltration of macrophages into the GVHD tissues. In vitro study showed that IL-17 could downregulate Th1 responses, possibly through inhibiting IL-12 production by donor macrophages. Depletion of macrophages in vivo diminished the protective effect of IL-17. Our results demonstrated the differential roles of adoptively transferred donor IL-17-producing CD4+T cells and IL-17 in the same acute GVHD model.
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Shoubao
authors.initials: S
authors.lastname: Ma
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Huanle
authors.initials: H
authors.lastname: Gong
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.|Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou 215006, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute for Immunology and School of Medicine, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Hematology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D018664:Interleukin-12