IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation
Acute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstra...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02724/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Huanle Gong Shoubao Ma Shuangzhu Liu Yonghao Liu Ziqi Jin Ying Zhu Yuan Song Lei Lei Bo Hu Yu Mei Hong Liu Yuejun Liu Yan Wu Chen Dong Yang Xu Depei Wu Haiyan Liu |
| spellingShingle |
Huanle Gong Shoubao Ma Shuangzhu Liu Yonghao Liu Ziqi Jin Ying Zhu Yuan Song Lei Lei Bo Hu Yu Mei Hong Liu Yuejun Liu Yan Wu Chen Dong Yang Xu Depei Wu Haiyan Liu IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation Frontiers in Immunology IL-17C Acute graft-vs.-host disease Treg cells intestinal barrier functions inflammation transplantation |
| author_facet |
Huanle Gong Shoubao Ma Shuangzhu Liu Yonghao Liu Ziqi Jin Ying Zhu Yuan Song Lei Lei Bo Hu Yu Mei Hong Liu Yuejun Liu Yan Wu Chen Dong Yang Xu Depei Wu Haiyan Liu |
| author_sort |
Huanle Gong |
| title |
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation |
| title_short |
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation |
| title_full |
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation |
| title_fullStr |
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation |
| title_full_unstemmed |
IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation |
| title_sort |
il-17c mitigates murine acute graft-vs.-host disease by promoting intestinal barrier functions and treg differentiation |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2018-11-01 |
| description |
Acute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model. In contrast, IL-17C overexpression ameliorated aGVHD. IL-17C deficiency increased intestinal epithelial permeability and elevated inflammatory cytokine production, leading to an enhanced aGVHD progression. Tregs was reduced in recipients of IL-17C−/− graft, whilst restored after IL-17C overexpression. Decreased Treg differentiation was abrogated after neutralizing IFN-γ, but not IL-6. Moreover, depletion of Tregs diminished the protective effect of IL-17C. Of note, patients with low IL-17C expression displayed higher aGVHD incidence together with poor overall survival, thereby IL-17C could be an independent risk factor for aGVHD development. Our results are the first demonstrating the protective role of IL-17C in aGVHD by promoting intestinal barrier functions and Treg differentiation in a MHC fully mismatched murine aGVHD model. IL-17C may serve as a novel biomarker and potential therapeutic target for aGVHD. |
| topic |
IL-17C Acute graft-vs.-host disease Treg cells intestinal barrier functions inflammation transplantation |
| url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02724/full |
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doaj-5ed09725bc744619b644d55de863cf5a2020-11-25T00:40:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02724406280IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg DifferentiationHuanle Gong0Shoubao Ma1Shuangzhu Liu2Yonghao Liu3Ziqi Jin4Ying Zhu5Yuan Song6Lei Lei7Bo Hu8Yu Mei9Hong Liu10Yuejun Liu11Yan Wu12Chen Dong13Yang Xu14Depei Wu15Haiyan Liu16Institute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaImmunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaImmunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaSchool of Radiation Medicine and Protection School for Radiological and Interdisciplinary Science, Soochow University, Suzhou, ChinaInstitute for Immunology and School of Medicine, Tsinghua University, Beijing, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Medical College of Soochow University, Soochow University, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaImmunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeAcute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model. In contrast, IL-17C overexpression ameliorated aGVHD. IL-17C deficiency increased intestinal epithelial permeability and elevated inflammatory cytokine production, leading to an enhanced aGVHD progression. Tregs was reduced in recipients of IL-17C−/− graft, whilst restored after IL-17C overexpression. Decreased Treg differentiation was abrogated after neutralizing IFN-γ, but not IL-6. Moreover, depletion of Tregs diminished the protective effect of IL-17C. Of note, patients with low IL-17C expression displayed higher aGVHD incidence together with poor overall survival, thereby IL-17C could be an independent risk factor for aGVHD development. Our results are the first demonstrating the protective role of IL-17C in aGVHD by promoting intestinal barrier functions and Treg differentiation in a MHC fully mismatched murine aGVHD model. IL-17C may serve as a novel biomarker and potential therapeutic target for aGVHD.https://www.frontiersin.org/article/10.3389/fimmu.2018.02724/fullIL-17CAcute graft-vs.-host diseaseTreg cellsintestinal barrier functionsinflammationtransplantation |