Gut defenders: How T-cell intraepithelial lymphocytes guard against colon cancer

In a recent study published in Science Immunology, researchers explore gene expression profiles of distinct populations of intraepithelial lymphocytes (IELs), particularly T-cell IELs (T-IELs), within different regions of the gastrointestinal (GI) tract.

Study: TCF-1 limits intraepithelial lymphocyte antitumor Q1 immunity in colorectal carcinoma. Image Credit: Kateryna Kon / Shutterstock.com

What are T-IELs?

T-IELs constantly survey the epithelium of the GI tract to sense commensal microorganisms and signs of infection through T-cell receptors (TCR) or other receptors that help maintain GI tract barrier integrity. 

Thus, T-IELs are critical in the communication network between the gut epithelium, microbiome, and diet. T-IELs are either thymic-derived, such as γδ and αβ T-cells, or induced, which develop from peripheral CD4+/CD8+ αβ T-cells. 

About the study

In the present study, researchers performed single-cell ribonucleic acid sequencing (scRNA-seq) of mouse IELs to understand how distinctive populations of IELs in the GI tract perform different immune functions. To this end, over 13,400 IELs isolated from the stomach, small intestine, cecum, and colon of naïve C57BL/6 mice were analyzed. 

Unsupervised clustering was used to investigate IEL diversity in the GI tract, especially T-cell clusters one, two, four, five, eight, and 10. Gene expression profiles of 200 up-and down-regulated genes in the colon and small intestine were also compared. 

Flow cytometry (FC) was used to measure IELs and the factors they expressed to regulate T-cell differentiation in the small and large intestines. Notably, IELs play a crucial role in defense against colon cancer.

The human small intestine primarily absorbs nutrition from food;

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