Appearance and disappearance of the mRNA signature characteristic of T reg cells in visceral adipose tissue: Age, diet, and PPARγ effects
Open accessAbstract
Significance: A unique population of Foxp3 + CD4 + regulatory T (T reg ) cells resides in visceral adipose tissue of lean mice. VAT T regs are important regulators of local and systemic inflammation and metabolism. Here, we show that the VAT T reg signature is imposed early in life, well before the typical age-dependent expansion of the adipose-tissue T reg population. VAT T regs in obese mice lose the signature typical of lean individuals but gain an additional set of over- and underrepresented transcripts. In striking parallel to a pathway recently elucidated in adipocytes, the obese mouse VAT T reg signature depends on phosphorylation of a specific residue of PPARγ. These findings are important to consider in designing drugs to target type 2 diabetes and other features of the “metabolic syndrome.”
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VAT Treg cells have a documented unique transcriptome and T cell receptor (TCR) repertoire.
“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 [33]
VAT Treg cells have a role in protecting from metabolic disease.
“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 [33]
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References 16 · Cited by 186
Research works printed but not linked: 11
- Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18(3):363-374.
- Mathis D (2013) Immunological goings-on in visceral adipose tissue. Cell Metab 17(6): 851-859.
- Cipolletta D (2014) Adipose tissue-resident regulatory T cells: Phenotypic specializa- tion, functions and therapeutic potential. Immunology 142(4):517-525.
- Cipolletta D, et al. (2012) PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486(7404):549-553.
- Choi JH, et al. (2011) Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation. Nature 477(7365):477-481.
- Choi JH, et al. (2010) Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature 466(7305):451-456.
- Banks AS, et al. (2014) An ERK/Cdk5 axis controls the diabetogenic actions of PPARγ. Nature, 10.1038/nature13887. · DOI
- Akiyama TE, et al. (2002) Conditional disruption of the peroxisome proliferator- activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol 22(8):2607-2619.
- Morita S, Kojima T, Kitamura T (2000) Plat-E: An efficient and stable system for transient packaging of retroviruses. Gene Ther 7(12):1063-1066.
- Holst J, et al. (2006) Generation of T-cell receptor retrogenic mice. Nat Protoc 1(1): 406-417.
- Naviaux RK, Costanzi E, Haas M, Verma IM (1996) The pCL vector system: rapid pro- duction of helper-free, high-titer, recombinant retroviruses. J Virol 70(8):5701-5705.
- Authors
- Cipolletta, D., Cohen, P., Spiegelman, B. M., Benoist, C., & Mathis, D.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-30
- Volume
- 112
- Issue
- 2
- Pages
- 482-487
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4299242
- OpenAlex
- W2117634860
- Cited by
- 186
- References
- 16
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 16 · 2023: 11 · 2022: 23 · 2021: 31 · 2020: 23 · 2019: 18 · 2018: 17 · 2017: 11 · 2016: 9 · 2015: 8
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK092541)
- Ellison Medical Foundation (None)
- JPB Foundation (None)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- regulatory T cells, Foxp3, visceral adipose tissue, transcriptome, PPARγ, obesity, aging, diet, epididymal adipose tissue, adipogenesis, type 2 diabetes, metabolic syndrome, inflammation, T cell receptor repertoire
- MeSH terms
- Aging, Animals, Cell Differentiation, Diet, Inflammation, Male, Mice, Mutant Strains, Obesity, Phosphorylation, RNA, Messenger, Thinness, Gene Expression Profiling, PPAR gamma, Intra-Abdominal Fat, T-Lymphocytes, Regulatory, Mice
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