Since their discovery over a decade ago, much has been learned regarding the importance and function of visceral adipose tissue (VAT)-resident regulatory T cells (Tregs). VAT Tregs play a critical role in controlling VAT inflammation and alleviating metabolic disease. However, this population is disrupted in obesity which exacerbates VAT inflammation and metabolic abnormalities. Therefore, understanding the factors governing the accumulation and maintenance of VAT Tregs, both at steady state and under disease conditions, is crucial for identifying the mechanisms underlying obesity-associated metabolic disease and developing novel therapies. Expansion and maintenance of the VAT Treg compartment is strongly influenced by factors in the local tissue microenvironment, including cytokines, T-cell receptor ligands, hormones, and various metabolites. This mini-review will primarily focus on recent advances in our understandings regarding the regulation of mouse epididymal VAT (eVAT) Tregs, which are the most thoroughly characterized VAT Treg population, by tissue microenvironmental factors and cellular metabolic processes. We will also briefly discuss the limited knowledge available regarding the regulation of mouse ovarian VAT (oVAT) Tregs and human omental VAT Tregs, highlight some lingering questions, and provide a prospective view on where the field is heading.
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http://dx.doi.org/10.1097/IN9.0000000000000013 | DOI Listing |
Sci Immunol
January 2025
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
Regulatory T cells (T) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored the metabolic pathways controlling the homeostasis, composition, and function of VAT T under normal and high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated in ST2 VAT T subsets.
View Article and Find Full Text PDFImmunol Rev
July 2024
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
Adipose tissue stores excess energy and produces a broad range of factors that regulate multiple physiological processes including systemic energy homeostasis. Visceral adipose tissue (VAT) plays a particularly important role in glucose metabolism as its endocrine function underpins food uptake and energy expenditure. Caloric excess triggers VAT inflammation which can impair insulin sensitivity and cause metabolic deregulation.
View Article and Find Full Text PDFImmunol Rev
July 2024
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Regulatory T cells (Tregs) within the visceral adipose tissue (VAT) play a crucial role in controlling tissue inflammation and maintaining metabolic health. VAT Tregs display a unique transcriptional profile and T cell receptor (TCR) repertoire, and closely interact with adipocytes, stromal cells, and other immune components within the local VAT microenvironment. However, in the context of obesity, there is a notable decline in VAT Tregs, resulting in heightened VAT inflammation and insulin resistance.
View Article and Find Full Text PDFFront Immunol
April 2024
Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan, Republic of Korea.
Regulatory T cells (Tregs) residing in visceral adipose tissue (VAT) play a pivotal role in regulating tissue inflammation and metabolic dysfunction associated with obesity. However, the specific phenotypic and functional characteristics of Tregs in obese VAT, as well as the regulatory mechanisms shaping them, remain elusive. This study demonstrates that obesity selectively reduces Tregs in VAT, characterized by restrained proliferation, heightened PD-1 expression, and diminished ST2 expression.
View Article and Find Full Text PDFLife Sci
January 2024
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal. Electronic address:
Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4 Treg cells. However, little is known about the CD8 Treg cells.
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