Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function

Transfer of splenocytes isolated from B6 mice into normal B6D2F1 mice induces acute graft-versus-host disease (aGVHD), resulting in the expansion of donor cytotoxic T lymphocytes that eliminate recipient B cells. The cytokine IL-22, secreted by Th1 cells, Th17 cells, and innate immune cells, is stru...

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Main Authors: Jianbo Wu, Jian Gu, Shun Zhou, Hao Lu, Yunjie Lu, Ling Lu, Xuehao Wang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/1605341
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author Jianbo Wu
Jian Gu
Shun Zhou
Hao Lu
Yunjie Lu
Ling Lu
Xuehao Wang
author_facet Jianbo Wu
Jian Gu
Shun Zhou
Hao Lu
Yunjie Lu
Ling Lu
Xuehao Wang
author_sort Jianbo Wu
collection DOAJ
description Transfer of splenocytes isolated from B6 mice into normal B6D2F1 mice induces acute graft-versus-host disease (aGVHD), resulting in the expansion of donor cytotoxic T lymphocytes that eliminate recipient B cells. The cytokine IL-22, secreted by Th1 cells, Th17 cells, and innate immune cells, is structurally related to IL-10. To investigate the association between IL-22 and aGVHD, an anti-mouse IL-22 antibody (IL-22Ab) was used to ablate IL-22 activity in a mouse aGVHD model. Administration of IL-22Ab significantly reduced the progression of aGVHD in B6D2F1 recipients of B6 grafts. IL-22Ab treatment also decreased the percentage of interferon-γ+ and tumor necrosis factor-α+ T cells but increased the number of forkhead box p3+ regulatory T cells (Tregs). In the presence of Tregs and donor CD11b+ cells, IL-22Ab protected against aGVHD. In vitro Treg induction was more efficient when CD4+CD25− T cells differentiated in the presence of CD11b+ cells obtained from IL-22Ab-treated GVHD mice, compared with cocultured untreated control cells. Finally, IL-22Ab modulated the expression of cytokines and costimulatory molecules in CD11b+ cells in aGVHD mice. We therefore conclude that IL-22Ab administration represents a viable approach for treating aGVHD.
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spelling doaj-art-b019406caa1e4ffa8887063811e515f62025-02-03T07:26:18ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/16053411605341Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell FunctionJianbo Wu0Jian Gu1Shun Zhou2Hao Lu3Yunjie Lu4Ling Lu5Xuehao Wang6Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaDepartment of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, National Health and Family Planning Commission, Nanjing, Jiangsu Province, ChinaTransfer of splenocytes isolated from B6 mice into normal B6D2F1 mice induces acute graft-versus-host disease (aGVHD), resulting in the expansion of donor cytotoxic T lymphocytes that eliminate recipient B cells. The cytokine IL-22, secreted by Th1 cells, Th17 cells, and innate immune cells, is structurally related to IL-10. To investigate the association between IL-22 and aGVHD, an anti-mouse IL-22 antibody (IL-22Ab) was used to ablate IL-22 activity in a mouse aGVHD model. Administration of IL-22Ab significantly reduced the progression of aGVHD in B6D2F1 recipients of B6 grafts. IL-22Ab treatment also decreased the percentage of interferon-γ+ and tumor necrosis factor-α+ T cells but increased the number of forkhead box p3+ regulatory T cells (Tregs). In the presence of Tregs and donor CD11b+ cells, IL-22Ab protected against aGVHD. In vitro Treg induction was more efficient when CD4+CD25− T cells differentiated in the presence of CD11b+ cells obtained from IL-22Ab-treated GVHD mice, compared with cocultured untreated control cells. Finally, IL-22Ab modulated the expression of cytokines and costimulatory molecules in CD11b+ cells in aGVHD mice. We therefore conclude that IL-22Ab administration represents a viable approach for treating aGVHD.http://dx.doi.org/10.1155/2018/1605341
spellingShingle Jianbo Wu
Jian Gu
Shun Zhou
Hao Lu
Yunjie Lu
Ling Lu
Xuehao Wang
Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
Journal of Immunology Research
title Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
title_full Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
title_fullStr Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
title_full_unstemmed Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
title_short Anti-IL-22 Antibody Attenuates Acute Graft-versus-Host Disease via Increasing Foxp3+ T Cell through Modulation of CD11b+ Cell Function
title_sort anti il 22 antibody attenuates acute graft versus host disease via increasing foxp3 t cell through modulation of cd11b cell function
url http://dx.doi.org/10.1155/2018/1605341
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