Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine

Abstract Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely dele...

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Autores principales:	Bola Aladegbami, Lauren Barron, James Bao, Jason Colasanti, Christopher R. Erwin, Brad W. Warner, Jun Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f002d43a0f434520a9951e5dbcbb5947
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spelling	oai:doaj.org-article:f002d43a0f434520a9951e5dbcbb59472021-12-02T11:52:27ZEpithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine10.1038/s41598-017-06070-w2045-2322https://doaj.org/article/f002d43a0f434520a9951e5dbcbb59472017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06070-whttps://doaj.org/toc/2045-2322Abstract Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.Bola AladegbamiLauren BarronJames BaoJason ColasantiChristopher R. ErwinBrad W. WarnerJun GuoNature 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 Bola Aladegbami Lauren Barron James Bao Jason Colasanti Christopher R. Erwin Brad W. Warner Jun Guo Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
description	Abstract Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.
format	article
author	Bola Aladegbami Lauren Barron James Bao Jason Colasanti Christopher R. Erwin Brad W. Warner Jun Guo
author_facet	Bola Aladegbami Lauren Barron James Bao Jason Colasanti Christopher R. Erwin Brad W. Warner Jun Guo
author_sort	Bola Aladegbami
title	Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
title_short	Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
title_full	Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
title_fullStr	Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
title_full_unstemmed	Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
title_sort	epithelial cell specific raptor is required for initiation of type 2 mucosal immunity in small intestine
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f002d43a0f434520a9951e5dbcbb5947
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Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine

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