The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
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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Cellular senescence: when bad things happen to good cells
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Inflammatory Mechanisms in Obesity
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PD-L2 is a second ligand for PD-1 and inhibits T cell activation
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Self-citationOverweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old
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Adipose-tissue plasticity in health and disease
Sakers, A. P., Siqueira, M. K. D., Seale, P., & Villanueva, C. J. (2022) · Cell · doi:10.1016/j.cell.2021.12.016 · Cited by 1,124
Wang, Z., Aguilar, E. G., Luna, J. I., Dunai, C., Khuat, L. T., Le, C. T., Mirsoian, A., Minnar, C. M., Stoffel, K. M., Sturgill, I. R., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0221-5 · Cited by 865
“T cells from tumor-bearing DIO mice upregulated anergy-, senescence, and TGF-β -associated genes as well as genes previously associated with obesity, diabetes and insulin-resistance 22 (Supplementary Fig.7a).”
Mittelbrunn, M., & Kroemer, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00927-z · Cited by 702
Clinical characteristics and outcomes of patients with severe COVID-19 with diabetes
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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
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