Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783619730065588224 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7719702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wanli ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT jinziqi ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT hubo ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT lvkangkang ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT leilei ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT liuyonghao ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT songyuan ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT zhuying ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT gonghuanle ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT xumimi ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT duyuanyuan ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT xuyang ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT liuhaiyan ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT wudepei ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses AT liuyuejun ilyaggravatesmurinechronicgraftversushostdiseasebyenhancingtandbcellresponses |