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TCR Transgenic Mice Reveal Stepwise, Multi-site Acquisition of the Distinctive Fat-Treg Phenotype
Open accessAbstract
Visceral adipose tissue (VAT) hosts a population of regulatory T (Treg) cells, with a unique phenotype, that controls local and systemic inflammation and metabolism. Generation of a T cell receptor transgenic mouse line, wherein VAT Tregs are highly enriched, facilitated study of their provenance, dependencies, and activities. We definitively established a role for T cell receptor specificity, uncovered an unexpected function for the primordial Treg transcription-factor, Foxp3, evidenced a cell-intrinsic role for interleukin-33 receptor, and ordered these dependencies within a coherent scenario. Genesis of the VAT-Treg phenotype entailed a priming step in the spleen, permitting them to exit the lymphoid organs and surveil nonlymphoid tissues, and a final diversification process within VAT, in response to microenvironmental cues. Understanding the principles of tissue-Treg biology is a prerequisite for precision-targeting strategies.
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“Tissue Treg cell precursor development is initiated in lymphatic organs and, thereby, follows a multistep model [375, 377, 452, 453].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [452]
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“As TCR signaling is thought to contribute to Treg cell accumulation in the brain and VAT 27,35”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [35]
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“VAT Treg cells were analyzed due to their documented unique transcriptome and T cell receptor (TCR) repertoire, as well as their role in protecting from metabolic disease 22,33-36 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [35]
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“VAT Treg cells were analyzed due to their documented unique transcriptome and T cell receptor (TCR) repertoire, as well as their role in protecting from metabolic disease 22,33-36 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [35]
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Metadata
- Authors
- Li, C., DiSpirito, J. R., Zemmour, D., Spallanzani, R. G., Kuswanto, W., Benoist, C., & Mathis, D.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Mathis, Diane
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 2
- Pages
- 285-299.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6046274
- OpenAlex
- W2806425229
- Cited by
- 231
- References
- 33
- Citations by year
- 2026: 8 · 2025: 31 · 2024: 41 · 2023: 20 · 2022: 35 · 2021: 31 · 2020: 28 · 2019: 29 · 2018: 8
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association (1-16-PDF-028, 1-17-PMF-005)
- National Institutes of Health (2R01 DK092541)
- JPB Foundation
- Boehringer Ingelheim (F30AG046045, T32-GM007753)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- visceral adipose tissue, regulatory T cells, T cell receptor transgenic mice, Foxp3, Treg differentiation, microenvironmental cues
- MeSH terms
- Interleukin-1 Receptor-Like 1 Protein, Animals, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Receptors, Antigen, T-Cell, RNA, Spleen, Receptors, Interleukin, Chromatin Assembly and Disassembly, PPAR gamma, Intra-Abdominal Fat, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Single-Cell Analysis, Transcriptome
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