Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg

Abstract C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observe...

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Autores principales:	Yulian Wang, Peilong Lai, Xiaomei Chen, Chang He, Xin Huang, Suxia Geng, Chenwei Luo, Suijing Wu, Wei Ling, Liye Zhong, Zesheng Lu, Peng Li, Jianyu Weng, Xin Du
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/968c082b8c6e4be28ec31bca05a9b95c
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spelling	oai:doaj.org-article:968c082b8c6e4be28ec31bca05a9b95c2021-12-02T11:53:00ZAttenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg10.1038/s41598-017-03700-12045-2322https://doaj.org/article/968c082b8c6e4be28ec31bca05a9b95c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03700-1https://doaj.org/toc/2045-2322Abstract C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg. In addition, an in vitro experiment revealed C5aR deficiency promoted the development of Treg whereas C5a activation abolished the differentiation of Treg. Importantly, we found C5aR blockade by PMX53 attenuated the pathology of cGVHD and improved the survival of cGVHD mice. PMX53 had a direct regulatory effect on Treg commitment and increased TGF-β1 expression. Thus, C5aR signaling may induce and intensify cGVHD by down-regulating Treg induction. The modulation of C5aR activation by PMX53 may provide a potential therapy for cGVHD.Yulian WangPeilong LaiXiaomei ChenChang HeXin HuangSuxia GengChenwei LuoSuijing WuWei LingLiye ZhongZesheng LuPeng LiJianyu WengXin DuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yulian Wang Peilong Lai Xiaomei Chen Chang He Xin Huang Suxia Geng Chenwei Luo Suijing Wu Wei Ling Liye Zhong Zesheng Lu Peng Li Jianyu Weng Xin Du Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
description	Abstract C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg. In addition, an in vitro experiment revealed C5aR deficiency promoted the development of Treg whereas C5a activation abolished the differentiation of Treg. Importantly, we found C5aR blockade by PMX53 attenuated the pathology of cGVHD and improved the survival of cGVHD mice. PMX53 had a direct regulatory effect on Treg commitment and increased TGF-β1 expression. Thus, C5aR signaling may induce and intensify cGVHD by down-regulating Treg induction. The modulation of C5aR activation by PMX53 may provide a potential therapy for cGVHD.
format	article
author	Yulian Wang Peilong Lai Xiaomei Chen Chang He Xin Huang Suxia Geng Chenwei Luo Suijing Wu Wei Ling Liye Zhong Zesheng Lu Peng Li Jianyu Weng Xin Du
author_facet	Yulian Wang Peilong Lai Xiaomei Chen Chang He Xin Huang Suxia Geng Chenwei Luo Suijing Wu Wei Ling Liye Zhong Zesheng Lu Peng Li Jianyu Weng Xin Du
author_sort	Yulian Wang
title	Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
title_short	Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
title_full	Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
title_fullStr	Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
title_full_unstemmed	Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
title_sort	attenuation of cgvhd by c5a/c5ar blockade is associated with increased frequency of treg
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/968c082b8c6e4be28ec31bca05a9b95c
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Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg

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