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dc.titleIL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
dc.contributor.authorWan, L.
dc.contributor.authorJin, Z.
dc.contributor.authorHu, B.
dc.contributor.authorLv, K.
dc.contributor.authorLei, L.
dc.contributor.authorLiu, Y.
dc.contributor.authorSong, Y.
dc.contributor.authorZhu, Y.
dc.contributor.authorGong, H.
dc.contributor.authorXu, M.
dc.contributor.authorDu, Y.
dc.contributor.authorXu, Y.
dc.contributor.authorLiu, H.
dc.contributor.authorWu, D.
dc.contributor.authorLiu, Y.
dc.identifier.citationWan, L., Jin, Z., Hu, B., Lv, K., Lei, L., Liu, Y., Song, Y., Zhu, Y., Gong, H., Xu, M., Du, Y., Xu, Y., Liu, H., Wu, D., Liu, Y. (2020). IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses. Frontiers in Immunology 11 : 559740. ScholarBank@NUS Repository.
dc.description.abstractIL-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-? producing CD4+ and CD8+ T cells through IL-27R? in recipient spleens, as this effect was diminished in IL-27R? 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. © Copyright © 2020 Wan, Jin, Hu, Lv, Lei, Liu, Song, Zhu, Gong, Xu, Du, Xu, Liu, Wu and Liu.
dc.publisherFrontiers Media S.A.
dc.rightsAttribution 4.0 International
dc.sourceScopus OA2020
dc.subjectB cell response
dc.subjectchronic graft-versus-host disease
dc.subjectT cell response
dc.subjectTfh cell
dc.subjectTreg cells
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.sourcetitleFrontiers in Immunology
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