Please use this identifier to cite or link to this item: https://doi.org/10.3389/fimmu.2018.02724
Title: IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation
Authors: Gong, Huanle
Ma, Shoubao 
Liu, Shuangzhu
Liu, Yonghao
Jin, Ziqi
ZHU YING 
Song, Yuan 
Lei, Lei
Hu, Bo
Mei, Yu 
Liu, Hong
Liu, Yuejun
Wu, Yan
Dong, Chen
Xu, Yang
Wu, Depei
Liu, Haiyan 
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
IL-17C
Acute graft-vs.-host disease
Treg cells
intestinal barrier functions
inflammation
transplantation
REGULATORY T-CELLS
BONE-MARROW-TRANSPLANTATION
TOTAL-BODY IRRADIATION
EPITHELIAL-CELLS
B-CELLS
INFLAMMATION
GVHD
TH1
ALLOANTIGEN
TOLERANCE
Issue Date: 26-Nov-2018
Publisher: FRONTIERS MEDIA SA
Citation: Gong, Huanle, Ma, Shoubao, Liu, Shuangzhu, Liu, Yonghao, Jin, Ziqi, ZHU YING, Song, Yuan, Lei, Lei, Hu, Bo, Mei, Yu, Liu, Hong, Liu, Yuejun, Wu, Yan, Dong, Chen, Xu, Yang, Wu, Depei, Liu, Haiyan (2018-11-26). IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation. FRONTIERS IN IMMUNOLOGY 9 (NOV). ScholarBank@NUS Repository. https://doi.org/10.3389/fimmu.2018.02724
Abstract: © 2007 - 2018 Frontiers Media S.A. Acute graft-vs.-host disease (aGVHD) is one of the major complications and results in high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). IL-17C is involved in many inflammatory immune disorders. However, the role of IL-17C in aGVHD remains unknown. Here we demonstrated that IL-17C deficiency in the graft significantly promoted alloreactive T cell responses and induced aggravated aGVHD compared with wildtype donors in a fully MHC-mismatched allo-HSCT model. In contrast, IL-17C overexpression ameliorated aGVHD. IL-17C deficiency increased intestinal epithelial permeability and elevated inflammatory cytokine production, leading to an enhanced aGVHD progression. Tregs was reduced in recipients of IL-17C -/- graft, whilst restored after IL-17C overexpression. Decreased Treg differentiation was abrogated after neutralizing IFN-γ, but not IL-6. Moreover, depletion of Tregs diminished the protective effect of IL-17C. Of note, patients with low IL-17C expression displayed higher aGVHD incidence together with poor overall survival, thereby IL-17C could be an independent risk factor for aGVHD development. Our results are the first demonstrating the protective role of IL-17C in aGVHD by promoting intestinal barrier functions and Treg differentiation in a MHC fully mismatched murine aGVHD model. IL-17C may serve as a novel biomarker and potential therapeutic target for aGVHD.
Source Title: FRONTIERS IN IMMUNOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/155214
ISSN: 1664-3224
1664-3224
DOI: 10.3389/fimmu.2018.02724
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