Single-cell atlas of colonic CD8+ T cells in ulcerative colitis

Colonic antigen-experienced lymphocytes such as tissue-resident memory CD8+ T cells can respond rapidly to repeated antigen exposure. However, their cellular phenotypes and the mechanisms by which they drive immune regulation and inflammation remain unclear. Here we compiled an unbiased atlas of hum...

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Main Authors: Corridoni, D, Antanaviciute, A, Gupta, T, Fawkner-Corbett, D, Aulicino, A, Jagielowicz, M, Parikh, K, Repapi, E, Taylor, S, Ishikawa, D, Hatano, R, Yamada, T, Xin, W, Slawinski, H, Bowden, R, Napolitani, G, Brain, O, Morimoto, C, Koohy, H, Simmons, A
Format: Journal article
Language:English
Published: Springer Nature 2020
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author Corridoni, D
Antanaviciute, A
Gupta, T
Fawkner-Corbett, D
Aulicino, A
Jagielowicz, M
Parikh, K
Repapi, E
Taylor, S
Ishikawa, D
Hatano, R
Yamada, T
Xin, W
Slawinski, H
Bowden, R
Napolitani, G
Brain, O
Morimoto, C
Koohy, H
Simmons, A
author_facet Corridoni, D
Antanaviciute, A
Gupta, T
Fawkner-Corbett, D
Aulicino, A
Jagielowicz, M
Parikh, K
Repapi, E
Taylor, S
Ishikawa, D
Hatano, R
Yamada, T
Xin, W
Slawinski, H
Bowden, R
Napolitani, G
Brain, O
Morimoto, C
Koohy, H
Simmons, A
author_sort Corridoni, D
collection OXFORD
description Colonic antigen-experienced lymphocytes such as tissue-resident memory CD8+ T cells can respond rapidly to repeated antigen exposure. However, their cellular phenotypes and the mechanisms by which they drive immune regulation and inflammation remain unclear. Here we compiled an unbiased atlas of human colonic CD8+ T cells in health and ulcerative colitis (UC) using single-cell transcriptomics with T-cell receptor repertoire analysis and mass cytometry. We reveal extensive heterogeneity in CD8+ T-cell composition, including expanded effector and post-effector terminally differentiated CD8+ T cells. While UC-associated CD8+ effector T cells can trigger tissue destruction and produce tumor necrosis factor (TNF)-α, post-effector cells acquire innate signatures to adopt regulatory functions that may mitigate excessive inflammation. Thus, we identify colonic CD8+ T-cell phenotypes in health and UC, define their clonal relationships and characterize terminally differentiated dysfunctional UC CD8+ T cells expressing IL-26, which attenuate acute colitis in a humanized IL-26 transgenic mouse model.
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spelling oxford-uuid:4fe7d6b5-f1c7-4d40-9784-e30db867182b2022-03-26T16:10:27ZSingle-cell atlas of colonic CD8+ T cells in ulcerative colitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4fe7d6b5-f1c7-4d40-9784-e30db867182bEnglishSymplectic ElementsSpringer Nature2020Corridoni, DAntanaviciute, AGupta, TFawkner-Corbett, DAulicino, AJagielowicz, MParikh, KRepapi, ETaylor, SIshikawa, DHatano, RYamada, TXin, WSlawinski, HBowden, RNapolitani, GBrain, OMorimoto, CKoohy, HSimmons, AColonic antigen-experienced lymphocytes such as tissue-resident memory CD8+ T cells can respond rapidly to repeated antigen exposure. However, their cellular phenotypes and the mechanisms by which they drive immune regulation and inflammation remain unclear. Here we compiled an unbiased atlas of human colonic CD8+ T cells in health and ulcerative colitis (UC) using single-cell transcriptomics with T-cell receptor repertoire analysis and mass cytometry. We reveal extensive heterogeneity in CD8+ T-cell composition, including expanded effector and post-effector terminally differentiated CD8+ T cells. While UC-associated CD8+ effector T cells can trigger tissue destruction and produce tumor necrosis factor (TNF)-α, post-effector cells acquire innate signatures to adopt regulatory functions that may mitigate excessive inflammation. Thus, we identify colonic CD8+ T-cell phenotypes in health and UC, define their clonal relationships and characterize terminally differentiated dysfunctional UC CD8+ T cells expressing IL-26, which attenuate acute colitis in a humanized IL-26 transgenic mouse model.
spellingShingle Corridoni, D
Antanaviciute, A
Gupta, T
Fawkner-Corbett, D
Aulicino, A
Jagielowicz, M
Parikh, K
Repapi, E
Taylor, S
Ishikawa, D
Hatano, R
Yamada, T
Xin, W
Slawinski, H
Bowden, R
Napolitani, G
Brain, O
Morimoto, C
Koohy, H
Simmons, A
Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title_full Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title_fullStr Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title_full_unstemmed Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title_short Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
title_sort single cell atlas of colonic cd8 t cells in ulcerative colitis
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