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IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses

IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine...

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Autores principales: Wan, Li, Jin, Ziqi, Hu, Bo, Lv, Kangkang, Lei, Lei, Liu, Yonghao, Song, Yuan, Zhu, Ying, Gong, Huanle, Xu, Mimi, Du, Yuanyuan, Xu, Yang, Liu, Haiyan, Wu, Depei, Liu, Yuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719702/
https://www.ncbi.nlm.nih.gov/pubmed/33329519
http://dx.doi.org/10.3389/fimmu.2020.559740
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author Wan, Li
Jin, Ziqi
Hu, Bo
Lv, Kangkang
Lei, Lei
Liu, Yonghao
Song, Yuan
Zhu, Ying
Gong, Huanle
Xu, Mimi
Du, Yuanyuan
Xu, Yang
Liu, Haiyan
Wu, Depei
Liu, Yuejun
author_facet Wan, Li
Jin, Ziqi
Hu, Bo
Lv, Kangkang
Lei, Lei
Liu, Yonghao
Song, Yuan
Zhu, Ying
Gong, Huanle
Xu, Mimi
Du, Yuanyuan
Xu, Yang
Liu, Haiyan
Wu, Depei
Liu, Yuejun
author_sort Wan, Li
collection PubMed
description IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4(+)Foxp3(+) regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4(+) and CD8(+) T cells through IL-27Rα in recipient spleens, as this effect was diminished in IL-27Rα deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS(+) T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells.
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spelling pubmed-77197022020-12-15 IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses Wan, Li Jin, Ziqi Hu, Bo Lv, Kangkang Lei, Lei Liu, Yonghao Song, Yuan Zhu, Ying Gong, Huanle Xu, Mimi Du, Yuanyuan Xu, Yang Liu, Haiyan Wu, Depei Liu, Yuejun Front Immunol Immunology IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4(+)Foxp3(+) regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4(+) and CD8(+) T cells through IL-27Rα in recipient spleens, as this effect was diminished in IL-27Rα deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS(+) T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells. Frontiers Media S.A. 2020-11-23 /pmc/articles/PMC7719702/ /pubmed/33329519 http://dx.doi.org/10.3389/fimmu.2020.559740 Text en Copyright © 2020 Wan, Jin, Hu, Lv, Lei, Liu, Song, Zhu, Gong, Xu, Du, Xu, Liu, Wu and Liu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wan, Li
Jin, Ziqi
Hu, Bo
Lv, Kangkang
Lei, Lei
Liu, Yonghao
Song, Yuan
Zhu, Ying
Gong, Huanle
Xu, Mimi
Du, Yuanyuan
Xu, Yang
Liu, Haiyan
Wu, Depei
Liu, Yuejun
IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title_full IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title_fullStr IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title_full_unstemmed IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title_short IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
title_sort il-y aggravates murine chronic graft-versus-host disease by enhancing t and b cell responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719702/
https://www.ncbi.nlm.nih.gov/pubmed/33329519
http://dx.doi.org/10.3389/fimmu.2020.559740
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