Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells

Abstract The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAP...

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Autores principales:	Yunpeng Hua, Yi Yang, Shaoli Sun, Stephen Iwanowycz, Caroline Westwater, Boris Reizis, Zihai Li, Bei Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e8b9cae5b49e48cc951ca9aa654fbc9b
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spelling	oai:doaj.org-article:e8b9cae5b49e48cc951ca9aa654fbc9b2021-12-02T15:05:50ZGut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells10.1038/s41598-017-02415-72045-2322https://doaj.org/article/e8b9cae5b49e48cc951ca9aa654fbc9b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02415-7https://doaj.org/toc/2045-2322Abstract The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c+ APCs in the gut immunity and tolerance is unknown. By a genetic strategy, we report here that selective deletion of gp96 from CD11c+ cells in mice results in alteration of dendritic cell and T cell subsets in the gut as well as loss of antigen-specific regulatory T cell induction in the mesenteric lymph nodes. Strikingly, these conditional gp96-null mice developed spontaneous colitis, had increased levels of systemic and fecal IgA, and were highly susceptible to chemical-induced colitis. Our findings for the first time demonstrate that gp96 is essential for CD11c+ cells to induce regulatory T cells and maintain gut homeostasis, illustrating the importance of protein immune chaperone in safeguarding against immune pathology.Yunpeng HuaYi YangShaoli SunStephen IwanowyczCaroline WestwaterBoris ReizisZihai LiBei LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yunpeng Hua Yi Yang Shaoli Sun Stephen Iwanowycz Caroline Westwater Boris Reizis Zihai Li Bei Liu Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
description	Abstract The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c+ APCs in the gut immunity and tolerance is unknown. By a genetic strategy, we report here that selective deletion of gp96 from CD11c+ cells in mice results in alteration of dendritic cell and T cell subsets in the gut as well as loss of antigen-specific regulatory T cell induction in the mesenteric lymph nodes. Strikingly, these conditional gp96-null mice developed spontaneous colitis, had increased levels of systemic and fecal IgA, and were highly susceptible to chemical-induced colitis. Our findings for the first time demonstrate that gp96 is essential for CD11c+ cells to induce regulatory T cells and maintain gut homeostasis, illustrating the importance of protein immune chaperone in safeguarding against immune pathology.
format	article
author	Yunpeng Hua Yi Yang Shaoli Sun Stephen Iwanowycz Caroline Westwater Boris Reizis Zihai Li Bei Liu
author_facet	Yunpeng Hua Yi Yang Shaoli Sun Stephen Iwanowycz Caroline Westwater Boris Reizis Zihai Li Bei Liu
author_sort	Yunpeng Hua
title	Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
title_short	Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
title_full	Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
title_fullStr	Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
title_full_unstemmed	Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells
title_sort	gut homeostasis and regulatory t cell induction depend on molecular chaperone gp96 in cd11c+ cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e8b9cae5b49e48cc951ca9aa654fbc9b
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_version_	1718388677763137536

Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells

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