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Small intestine and colon tissue-resident memory CD8<sup>+</sup> T cells exhibit molecular heterogeneity and differential dependence on Eomes.

Immunity · 2023 · Vol. 56 (1) · pp. 207-223.e8

Abstract

Tissue-resident memory CD8<sup>+</sup> T (T<sub>RM</sub>) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. T<sub>RM</sub> 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<sub>RM</sub> cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal T<sub>RM</sub> 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<sub>RM</sub> cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established T<sub>RM</sub> 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<sub>RM</sub> cells.

Publication Types

["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't", "Research Support, U.S. Gov't, Non-P.H.S."]

Keywords

MeSH Terms

["CD8-Positive T-Lymphocytes", "Memory T Cells", "Immunologic Memory", "Intestine, Small", "Colon"]

Funding

S10 OD026929 NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
P30 CA023100 NCI NIH HHS (United States)
P30 DK120515 NIDDK NIH HHS (United States)
R01 AI129973 NIAID NIH HHS (United States)
P01 AI132122 NIAID NIH HHS (United States)
I01 CX002396 CSRD VA (United States)
R01 AI123202 NIAID NIH HHS (United States)
I01 BX005106 BLRD VA (United States)
T32 AR064194 NIAMS NIH HHS (United States)
T32 DK007202 NIDDK NIH HHS (United States)

Linked Datasets (3)

GSE205549 GSE via ncbi_elink
GEO

Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [scATAC-seq]

Mus musculus
5 data files
FileTypeSize
1_CIEL_S1_L001_R1_001.fastq.gz ATAC-seq 19.4 GB
2_CLPL_S2_L001_R1_001.fastq.gz ATAC-seq 16.5 GB
4_SI_IEL_S4_L001_R1_001.fastq.gz ATAC-seq 22.1 GB
6_SI_LPL_S6_L001_R1_001.fastq.gz ATAC-seq 12.8 GB
SRR19560828.lite ATAC-seq 22.1 GB
GSE205941 GSE via ncbi_elink
GEO

Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [CITE-seq]

Mus musculus
16 data files
FileTypeSize
3_19_NE_CIEL_CD45_1_2_ADT_S68_L002_R1_001.fastq.gz OTHER 415.0 MB
3_19_NE_CIEL_CD45_1_2_RNA_S68_L003_R1_001.fastq.gz OTHER 2.7 GB
3_19_NE_CIEL_CD45_1_ADT_S67_L002_R1_001.fastq.gz OTHER 653.8 MB
3_19_NE_CIEL_CD45_1_RNA_S67_L003_R1_001.fastq.gz OTHER 4.2 GB
3_19_NE_CLPL_CD45_1_2_ADT_S66_L002_R1_001.fastq.gz OTHER 1.5 GB
3_19_NE_CLPL_CD45_1_2_RNA_S66_L003_R1_001.fastq.gz OTHER 4.4 GB
3_19_NE_CLPL_CD45_1_ADT_S65_L002_R1_001.fastq.gz OTHER 336.6 MB
3_19_NE_CLPL_CD45_1_RNA_S65_L003_R1_001.fastq.gz OTHER 3.0 GB
3_19_NE_SIIEL_CD45_1_2_ADT_S62_L002_R1_001.fastq.gz OTHER 3.9 GB
3_19_NE_SIIEL_CD45_1_2_RNA_S62_L003_R1_001.fastq.gz OTHER 4.8 GB
3_19_NE_SIIEL_CD45_1_ADT_S61_L002_R1_001.fastq.gz OTHER 5.2 GB
3_19_NE_SIIEL_CD45_1_RNA_S61_L003_R1_001.fastq.gz OTHER 5.4 GB
3_19_NE_SILPL_CD45_1_2_ADT_S64_L002_R1_001.fastq.gz OTHER 715.3 MB
3_19_NE_SILPL_CD45_1_2_RNA_S64_L003_R1_001.fastq.gz OTHER 2.2 GB
3_19_NE_SILPL_CD45_1_ADT_S63_L002_R1_001.fastq.gz OTHER 3.0 GB
3_19_NE_SILPL_CD45_1_RNA_S63_L003_R1_001.fastq.gz OTHER 3.9 GB
GSE205942 GSE via ncbi_elink
GEO

Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin

Mus musculus

Potentially Related Datasets (2)

These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.

E-MTAB-9532 E-MTAB ArrayExpress

Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence …

Analysis Pipelines (3)

scRNA-seq geo_data_processing GSE205549
scRNA-seq geo_data_processing GSE205941
scRNA-seq geo_data_processing GSE205942