Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes

Yun Hsuan Lin; Han G Duong; Abigail E Limary; Eleanor S Kim; Paul Hsu; Shefali A Patel; William H Wong; Cynthia S Indralingam; Yi Chia Liu; Priscilla Yao; Natalie R Chiang; Sara A Vandenburgh; Taylor R Anderson; Jocelyn G Olvera; Amir Ferry; Kennidy K Takehara; Wenhao Jin; Matthew S Tsai; Gene W Yeo; Ananda W Goldrath; John T Chang

doi:10.1016/j.immuni.2022.12.007

Small intestine and colon tissue-resident memory CD8⁺ T cells exhibit molecular heterogeneity and differential dependence on Eomes

Immunity. 2023 Jan 10;56(1):207-223.e8. doi: 10.1016/j.immuni.2022.12.007. Epub 2022 Dec 28.

Authors

Yun Hsuan Lin¹, Han G Duong¹, Abigail E Limary¹, Eleanor S Kim¹, Paul Hsu¹, Shefali A Patel¹, William H Wong¹, Cynthia S Indralingam¹, Yi Chia Liu¹, Priscilla Yao¹, Natalie R Chiang¹, Sara A Vandenburgh¹, Taylor R Anderson¹, Jocelyn G Olvera¹, Amir Ferry², Kennidy K Takehara², Wenhao Jin³, Matthew S Tsai¹, Gene W Yeo⁴, Ananda W Goldrath², John T Chang⁵

Affiliations

¹ Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
² Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
³ Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁵ Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, Jennifer Moreno Department of Veteran Affairs Medical Center, San Diego, CA 92161, USA. Electronic address: changj@ucsd.edu.

Abstract

Tissue-resident memory CD8⁺ T (T_RM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. T_RM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing T_RM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal T_RM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses T_RM cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established T_RM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal T_RM cells.

Keywords: Eomes; colon; single-cell ATAC-sequencing; single-cell RNA-sequencing; small intestine; tissue-resident memory CD8(+) T cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

CD8-Positive T-Lymphocytes* / metabolism
Colon
Immunologic Memory
Intestine, Small
Memory T Cells*

Abstract

Publication types

MeSH terms

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