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

Daniele Corridoni, Agne Antanaviciute, Tarun Gupta, David Fawkner-Corbett, Anna Aulicino, Marta Jagielowicz, Kaushal Parikh, Emmanouela Repapi, Steve Taylor, Dai Ishikawa, Ryo Hatano, Taketo Yamada, Wei Xin, Hubert Slawinski, Rory Bowden, Giorgio Napolitani, Oliver Brain, Chikao Morimoto, Hashem Koohy, Alison Simmons

doi:10.1038/s41591-020-1003-4

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. Multimodal single-cell profiling reveals heterogeneity of colonic CD8+ T cells in patients with ulcerative colitis, including expansion of a chronically activated IL-26-expressing subpopulation with innate-like features.

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

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