Tissue regulatory T cells: regulatory chameleons
Open accessAbstract
The FOXP3+CD4+ regulatory T (T reg) cells located in non-lymphoid tissues differ in phenotype and function from their lymphoid organ counterparts. Tissue T reg cells have distinct transcriptomes, T cell receptor repertoires and growth and survival factor dependencies that arm them to survive and operate in their home tissue. Their functions extend beyond immune surveillance to tissue homeostasis, including regulation of local and systemic metabolism, promotion of tissue repair and regeneration, and control of the proliferation, differentiation and fate of non-lymphoid cell progenitors. T reg cells in diverse tissues share a common FOXP3+CD4+ precursor located within lymphoid organs. This precursor undergoes definitive specialization once in the home tissue, following a multilayered array of common and tissue-distinct transcriptional programmes. Our deepening knowledge of tissue T reg cell biology will inform ongoing attempts to harness T reg cells for precision immunotherapeutics.
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Treg cells in tissues have distinct transcriptional signatures.
“Treg cells in tissues have distinct transcriptional signatures 31 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [31]
Adhesion to the epithelium is thought to be essential for Th17 induction, because rat-derived SFB that does not adhere to mouse small intestinal epithelium fails to induce intestinal Th17 cells.
“Adhesion to the epithelium is thought to be essential for the induction of Th17 cells, as rat-derived SFB, that does not adhere to the small intestinal epithelium in mouse hosts, failed to induce intestinal Th17 cells”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [73]
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Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet
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Understanding vertebrate immunity through comparative immunology
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Aged hematopoietic stem cells entrap regulatory T cells to create a prosurvival microenvironment
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The immunoregulatory roles of non-haematopoietic cells in the kidney
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An integrated transcription factor framework for Treg identity and diversity
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CCR8 + decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy
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Eras of designer Tregs: Harnessing synthetic biology for immune suppression
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The emerging role of tissue regulatory T cells in tissue repair and regeneration
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Interpreting Immunoregulation in Lung Fibrosis: A New Branch of the Immune Model
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The potential of regulatory T cell-based therapies for alopecia areata
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Dysregulated Treg repair responses lead to chronic rejection after heart transplantation
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Interactions between islets and regulatory immune cells in health and type 1 diabetes
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TNFR2 Costimulation Differentially Impacts Regulatory and Conventional CD4+ T-Cell Metabolism
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Treg suppression of immunity within inflamed allogeneic grafts
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The Nr4a family regulates intrahepatic Treg proliferation and liver fibrosis in MASLD models
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Regulation of Treg Cell Metabolism and Function in Non-Lymphoid Tissues
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The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis
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Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration
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Thymic self-antigen expression for immune tolerance and surveillance
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Moving to the Outskirts: Interplay Between Regulatory T Cells and Peripheral Tissues
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Regulation of Progression and Resolution of Liver Fibrosis by Immune Cells
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Promises and Pitfalls of Next-Generation Treg Adoptive Immunotherapy
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The partitioning of TCR repertoires by thymic selection
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Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics
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ILC2s – development, divergence, dispersal
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Treg cells require Izumo1R to regulate γδT cell-driven inflammation in the skin
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- Authors
- Muñoz-Rojas, A. R., & Mathis, D.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Mathis, Diane
- Venue
- Nature Reviews Immunology
- Published
- 2021-03-26
- Volume
- 21
- Issue
- 9
- Pages
- 597-611
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC8403160
- OpenAlex
- W3136492352
- Cited by
- 281
- References
- 123
- Citations by year
- 2026: 59 · 2025: 61 · 2024: 61 · 2023: 47 · 2022: 40 · 2021: 13
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (RC2DK116691, R01DK092541)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070334)
- 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
- CD4+ Foxp3+ T cells, non-lymphoid tissues, T cell receptor repertoire, immune surveillance, tissue homeostasis, local metabolism, tissue repair and regeneration, immunotherapy
- MeSH terms
- Animals, Female, Homeostasis, Humans, Male, Receptors, Antigen, T-Cell, Skin, Models, Immunological, Muscle, Skeletal, Intra-Abdominal Fat, T-Lymphocytes, Regulatory, Mice, Transcriptome
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