Common and Exclusive Features of Intestinal Intraepithelial γδ T Cells and Other γδ T Cell Subsets

Apostolov, Apostol; Hamani, Miriame; Hernández-Vargas, Héctor; Igalouzene, Ramdane; Guyennon, Alexandre; Fesneau, Olivier; Marie, Julien C.; Soudja, Saïdi M.

doi:10.4049/immunohorizons.2200046

Cited by 3 publications

(2 citation statements)

References 77 publications

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“…Tex 1 cells are actively proliferating, indicated by their expression of MKI67, TOP2A, and other cell cycle-related genes such as TUBA1B, MCM3, MCM5, and MCM6. In contrast, Tex 2 cells uniquely expressed IKZF2 (Helios), a transcription factor found in Tregs, where its deficiency downregulates Foxp3 and adopts a more effector-like function 118 , specific to murine intraepithelial γδ T cells 119 . It also shows increased levels of ZNF683 (Hobit) and PRDM1 (Blimp-1), transcription factors associated with effector function and exhaustion.…”

Section: Human Colorectal Cancer-related γδ T Cells Are Heterogeneousmentioning

confidence: 99%

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

Ran,

Trapecar,

Brubaker

2024

Preprint

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Gamma delta (γδ) T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment (TME) of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing (scRNA-seq) datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including Teff, TRM, Tpex, and Tex, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology.

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Section: Human Colorectal Cancer-related γδ T Cells Are Heterogeneousmentioning

confidence: 99%

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

Ran,

Trapecar,

Brubaker

2024

Preprint

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“…The adaptive immune system in the gut mucosa comprises mainly intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) [51]. Among the IELs, γδ T cells are a distinct subset of T cells because they express the Helios transcription factor [52]. γδ T lymphocytes inhibit the mucosal dissemination of bacteria by secreting pro-inflammatory cytokines and antimicrobial proteins [53,54].…”

Section: Interaction Between Gut Microbiota and Adaptive Immune Systemmentioning

confidence: 99%

Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy

et al. 2023

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Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota–immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota–immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.

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Nurturing the phenotype: Environmental signals and transcriptional regulation of intestinal γδ T cells

Vogg*,

Winkler

2024

Eur J Immunol

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The intestinal epithelium harbours a unique lymphocyte population, the intraepithelial lymphocytes (IELs). A large fraction of IELs is represented by γδ T cells. Their role in epithelial homeostasis and immune response is well documented, but a conclusive view of their developmental pathway is still missing. In this review, we discuss the existing literature as well as recent advances regarding the tissue adaptation of γδ IELs, both for the characteristic cytotoxic subset and the newly described noncytotoxic subset. We particularly highlight the environmental cues and the transcriptional regulation that equip γδ T cells with their IEL phenotype.

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Common and Exclusive Features of Intestinal Intraepithelial γδ T Cells and Other γδ T Cell Subsets

Cited by 3 publications

References 77 publications

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy

Nurturing the phenotype: Environmental signals and transcriptional regulation of intestinal γδ T cells

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