In:
Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-11-23)
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-α producing CD4 + and CD8 + T cells through IL-27R α in recipient spleens, as this effect was diminished in IL-27R α 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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2020.559740
DOI:
10.3389/fimmu.2020.559740.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2020
detail.hit.zdb_id:
2606827-8
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