Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes

Tissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural T-IEL, which are developmentally targeted to the intesti...

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Autores principales:	Alejandro J Brenes, Maud Vandereyken, Olivia J James, Harriet Watt, Jens Hukelmann, Laura Spinelli, Dina Dikovskaya, Angus I Lamond, Mahima Swamy
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	T lymphocytes intestinal immunity proteomics immunometabolism Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6e624ebedfb24dd29e8cecd5bdc4e781
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spelling	oai:doaj.org-article:6e624ebedfb24dd29e8cecd5bdc4e7812021-12-01T10:53:51ZTissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes10.7554/eLife.700552050-084Xe70055https://doaj.org/article/6e624ebedfb24dd29e8cecd5bdc4e7812021-09-01T00:00:00Zhttps://elifesciences.org/articles/70055https://doaj.org/toc/2050-084XTissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural T-IEL, which are developmentally targeted to the intestine. While the processes driving T-IEL development have been elucidated, the precise roles of the different subsets and the processes driving activation and regulation of these cells remain unclear. To gain functional insights into these enigmatic cells, we used high-resolution, quantitative mass spectrometry to compare the proteomes of induced T-IEL and natural T-IEL subsets, with naive CD8+ T cells from lymph nodes. This data exposes the dominant effect of the gut environment over ontogeny on T-IEL phenotypes. Analyses of protein copy numbers of >7000 proteins in T-IEL reveal skewing of the cell surface repertoire towards epithelial interactions and checkpoint receptors; strong suppression of the metabolic machinery indicating a high energy barrier to functional activation; upregulated cholesterol and lipid metabolic pathways, leading to high cholesterol levels in T-IEL; suppression of T cell antigen receptor signalling and expression of the transcription factor TOX, reminiscent of chronically activated T cells. These novel findings illustrate how T-IEL integrate multiple tissue-specific signals to maintain their homeostasis and potentially function.Alejandro J BrenesMaud VandereykenOlivia J JamesHarriet WattJens HukelmannLaura SpinelliDina DikovskayaAngus I LamondMahima SwamyeLife Sciences Publications LtdarticleT lymphocytesintestinal immunityproteomicsimmunometabolismMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	T lymphocytes intestinal immunity proteomics immunometabolism Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	T lymphocytes intestinal immunity proteomics immunometabolism Medicine R Science Q Biology (General) QH301-705.5 Alejandro J Brenes Maud Vandereyken Olivia J James Harriet Watt Jens Hukelmann Laura Spinelli Dina Dikovskaya Angus I Lamond Mahima Swamy Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
description	Tissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural T-IEL, which are developmentally targeted to the intestine. While the processes driving T-IEL development have been elucidated, the precise roles of the different subsets and the processes driving activation and regulation of these cells remain unclear. To gain functional insights into these enigmatic cells, we used high-resolution, quantitative mass spectrometry to compare the proteomes of induced T-IEL and natural T-IEL subsets, with naive CD8+ T cells from lymph nodes. This data exposes the dominant effect of the gut environment over ontogeny on T-IEL phenotypes. Analyses of protein copy numbers of >7000 proteins in T-IEL reveal skewing of the cell surface repertoire towards epithelial interactions and checkpoint receptors; strong suppression of the metabolic machinery indicating a high energy barrier to functional activation; upregulated cholesterol and lipid metabolic pathways, leading to high cholesterol levels in T-IEL; suppression of T cell antigen receptor signalling and expression of the transcription factor TOX, reminiscent of chronically activated T cells. These novel findings illustrate how T-IEL integrate multiple tissue-specific signals to maintain their homeostasis and potentially function.
format	article
author	Alejandro J Brenes Maud Vandereyken Olivia J James Harriet Watt Jens Hukelmann Laura Spinelli Dina Dikovskaya Angus I Lamond Mahima Swamy
author_facet	Alejandro J Brenes Maud Vandereyken Olivia J James Harriet Watt Jens Hukelmann Laura Spinelli Dina Dikovskaya Angus I Lamond Mahima Swamy
author_sort	Alejandro J Brenes
title	Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
title_short	Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
title_full	Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
title_fullStr	Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
title_full_unstemmed	Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
title_sort	tissue environment, not ontogeny, defines murine intestinal intraepithelial t lymphocytes
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/6e624ebedfb24dd29e8cecd5bdc4e781
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_version_	1718405238536273920

Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes

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