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Obesity accelerates T cell senescence in murine visceral adipose tissue
Open accessAbstract
Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Although changes in T cell function associated with visceral obesity are thought to affect chronic VAT inflammation, the specific features of these changes remain elusive. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44hiCD62LloCD4+ T cells that constitutively express PD-1 and CD153 in a B cell-dependent manner in VAT. These cells possessed characteristics of cellular senescence and showed a strong activation of Spp1 (encoding osteopontin [OPN]) in VAT. Upon T cell receptor stimulation, these T cells also produced large amounts of OPN in a PD-1-resistant manner in vitro. The features of CD153+PD-1+CD44hiCD4+ T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153+PD-1+CD44hiCD4+ T cell population that accumulates in the VAT of HFD-fed obese mice causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.
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“TNSF8+PDCD1+CD44hiCD4+ (CD153+PDCD+CD44hiCD4+) T cells accumulate in adipose tissue in obesity and show senescence features, including increased expression of SPP1, CDKN2A and CDKN1A and decreased expression of SATB1, DUSP10 and EEF1A1128.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [128]
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Influential
Metadata
- Authors
- Shirakawa, K., Yan, X., Shinmura, K., Endo, J., Kataoka, M., Katsumata, Y., Yamamoto, T., Anzai, A., Isobe, S., Yoshida, N., Itoh, H., Manabe, I., Sekai, M., Hamazaki, Y., Fukuda, K., Minato, N., & Sano, M.
- Affiliations
- Keio University (JP)
- Shanghai Jiao Tong University (CN)
- Hyogo Medical University (JP)
- The University of Tokyo (JP)
- Kyoto University (JP)
- Corresponding author
- Minato, Nagahiro
- Sano, Motoaki
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2016-11-07
- Volume
- 126
- Issue
- 12
- Pages
- 4626-4639
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5127667
- OpenAlex
- W2548313353
- Cited by
- 271
- References
- 54
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 30 · 2023: 34 · 2022: 31 · 2021: 43 · 2020: 28 · 2019: 24 · 2018: 32 · 2017: 16
- FWCI
- 22.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Keio University
- Japan Foundation for Aging and Health
- National Institutes of Health
- Japan Society for the Promotion of Science (15H01160, 22590814, 24111008, 15H04825, 24111001, 15K19125)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- visceral obesity, T cell senescence, visceral adipose tissue inflammation, osteopontin, PD-1, CD4+ T cells, high-fat diet, immunosenescence, insulin resistance, CD44, L-selectin, adoptive transfer
- MeSH terms
- Animals, B-Lymphocytes, Dietary Fats, Inflammation, Obesity, Receptors, Antigen, T-Cell, CD4-Positive T-Lymphocytes, Antigens, CD, Cellular Senescence, Mice, Knockout, Intra-Abdominal Fat, Mice, Osteopontin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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