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Title: IL-Y Aggravates Murine Chronic Graft-Versus-Host Disease by Enhancing T and B Cell Responses
Authors: Wan, 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.
Keywords: B cell response
chronic graft-versus-host disease
T cell response
Tfh cell
Treg cells
Issue Date: 2020
Publisher: Frontiers Media S.A.
Citation: Wan, 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.
Rights: Attribution 4.0 International
Abstract: 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-? 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.
Source Title: Frontiers in Immunology
ISSN: 16643224
DOI: 10.3389/fimmu.2020.559740
Rights: Attribution 4.0 International
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