Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/...

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Autores principales:	Wen Zhang, Yao Wang, Chuanwei Li, Yu Xu, Xia Wang, Di Wu, Zhan Gao, Hang Qian, Zaichun You, Zhiren Zhang, Binfeng He, Guansong Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	acute lung injury (ALI) eCIRP EPOR Rab26 GTPase macrophages Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/147d7aefa2044105ad2fac998052ef78
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spelling	oai:doaj.org-article:147d7aefa2044105ad2fac998052ef782021-12-01T21:50:13ZExtracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury1664-322410.3389/fimmu.2021.768435https://doaj.org/article/147d7aefa2044105ad2fac998052ef782021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.768435/fullhttps://doaj.org/toc/1664-3224Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.Wen ZhangYao WangChuanwei LiYu XuXia WangDi WuZhan GaoHang QianZaichun YouZhiren ZhangBinfeng HeBinfeng HeGuansong WangFrontiers Media S.A.articleacute lung injury (ALI)eCIRPEPORRab26 GTPasemacrophagesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute lung injury (ALI) eCIRP EPOR Rab26 GTPase macrophages Immunologic diseases. Allergy RC581-607
spellingShingle	acute lung injury (ALI) eCIRP EPOR Rab26 GTPase macrophages Immunologic diseases. Allergy RC581-607 Wen Zhang Yao Wang Chuanwei Li Yu Xu Xia Wang Di Wu Zhan Gao Hang Qian Zaichun You Zhiren Zhang Binfeng He Binfeng He Guansong Wang Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
description	Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.
format	article
author	Wen Zhang Yao Wang Chuanwei Li Yu Xu Xia Wang Di Wu Zhan Gao Hang Qian Zaichun You Zhiren Zhang Binfeng He Binfeng He Guansong Wang
author_facet	Wen Zhang Yao Wang Chuanwei Li Yu Xu Xia Wang Di Wu Zhan Gao Hang Qian Zaichun You Zhiren Zhang Binfeng He Binfeng He Guansong Wang
author_sort	Wen Zhang
title	Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_short	Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_full	Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_fullStr	Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_full_unstemmed	Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury
title_sort	extracellular cirp-impaired rab26 restrains epor-mediated macrophage polarization in acute lung injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/147d7aefa2044105ad2fac998052ef78
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Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury

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