γδ T cells in homeostasis and host defence of epithelial barrier tissues
Open accessAbstract
Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.
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Mouse γδ T cell subsets are distinguished by different TCR Vγ chains, whereas human γδ T cell subsets are often distinguished by Vγ chain usage.
“The mouse γδ T cell subsets are distinguished by different T cell receptor(TCR) Vγ chains, whereas human γδ T cell subsets are often distinguished by Vγ chain usage (2).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [2]
The section “γδ T cells in the epithelial layer of skin and intestine” supports the mouse half of the claim but says human subsets are often distinguished by Vδ usage, not Vγ usage. No page number is provided in our copy. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredCertain subsets of γδ T cells are present in much higher proportions (10-100%) in epithelial tissues, such as the reproductive tract, skin epidermis, and gastrointestinal tract.
“However, certain subsets of γδ T cells are present in much higher proportions (10–100%) in epithelial tissues, such as the reproductive tract, skin epidermis, and gastrointestinal tract (2).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [2]
There is no direct equivalent of DETCs in human skin as the immune cell composition of the epidermis is subject to species-specific differences.
“There is no direct equivalent of DETCs in human skin as the immune cell composition of the epidermis is subject to species-specific differences (2).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [2]
The maintenance of steady-state numbers of DETC is dependent on epithelial cell-derived IL-15, insulin-like growth factor I (IGF1) produced by DETC itself, and through the transcription factor aryl hydrocarbon receptor (AHR) ligand.
“The maintenance of steady-state numbers of DETC is dependent on epithelial cell-derived IL-15, insulin-like growth factor I (IGF1) produced by DETC itself, and through the transcription factor aryl hydrocarbon receptor (AHR) ligand (2).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [2]
In vivo anti-TCR γδ administration is associated with internalization of TCR γδ without actual loss of meningeal γδ T cells.
“In vivo administration of anti-TCR γδ monoclonal antibodies was associated with internalization of TCR γδ, without actual loss of the meningeal γδ T cells (Fig. 4a, Extended Data Fig. 3a-b), similar to what has been previously shown in the intestine18.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [18]
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Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair
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“For instance, DETC were also previously shown to promote tissue repair (Nielsen et al., 2017) but were not required for the tissue repair effect of S. epidermidis, supporting the idea that these two cell subsets play distinct roles in this process.”
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Development, Homeostasis, and Functions of Intestinal Intraepithelial Lymphocytes
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Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses
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“In human skin, gd T cells dominate in both the dermis and the epidermis, but gd T cells are present in both compartments (2).”
BackgroundInfluentialCoeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder
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Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice
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- Authors
- Nielsen, M. M., Witherden, D. A., & Havran, W. L.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Havran, Wendy L.
- Venue
- Nature Reviews Immunology
- Published
- 2017-09-18
- Volume
- 17
- Issue
- 12
- Pages
- 733-745
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC5771804
- OpenAlex
- W2754761629
- Cited by
- 479
- References
- 145
- Citations by year
- 2026: 36 · 2025: 39 · 2024: 54 · 2023: 72 · 2022: 56 · 2021: 59 · 2020: 77 · 2019: 55 · 2018: 29 · 2017: 2
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- Lundbeckfonden
- Danmarks Frie Forskningsfond
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R21AI129401, R01AI036964, R01AI064811)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- γδ T cells, intraepithelial T cells, epithelial barrier function, tissue homeostasis, tissue repair, skin, intestine, epidermis, microbiome, microbial tolerance, host defense, pathogen clearance, butyrophilin
- MeSH terms
- Butyrophilins, Mucosal-Associated Invariant T Cells, Intraepithelial Lymphocytes, Animals, Cell Differentiation, Epithelium, Gene Expression Regulation, Homeostasis, Humans, Intestinal Mucosa, Signal Transduction, Biomarkers, Receptors, Antigen, T-Cell, gamma-delta, Host-Pathogen Interactions
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