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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529
Inflammatory links between obesity and metabolic disease
Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319
Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230
Self-citationOverweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old
Adams, K. F., Schatzkin, A. G., Harris, T. B., Kipnis, V., Mouw, T., Ballard-Barbash, R. R., Hollenbeck, A. R., & Leitzmann, M. F. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055643 · Cited by 2,147
Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145
Body Fat Distribution and Risk of Cardiovascular Disease: An Update
Després, J.-P. (2012) · Circulation · doi:10.1161/circulationaha.111.067264 · Cited by 1,481
Research works printed but not linked: 1
- 10.1038/ni0107-19 · DOI
Cited by
Sorted by citations
Items 101–200 of 268
Senescent T Cell Induces Brown Adipose Tissue “Whitening” Via Secreting IFN-γ
Pan, X., Yao, K.-L., Yang, Y., Ge, Q., Zhang, R., Gao, P., Ruan, C., & Wu, F. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.637424 · Cited by 41
Obesity in geroscience — is cellular senescence the culprit?
Franceschi, C. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.213 · Cited by 39
Cellular Senescence in Obesity and Associated Complications: a New Therapeutic Target
Narasimhan, A., Flores, R. R., Camell, C. D., Bernlohr, D., Robbins, P. D., & Niedernhofer, L. J. (2022) · Current Diabetes Reports · doi:10.1007/s11892-022-01493-w · Cited by 40
“Obesity increases the SnC accumulation in the liver [52, 97, 98].”
BackgroundT-cell senescence: A crucial player in autoimmune diseases
Lu, Y., Ruan, Y., Pan, H., Rui, K., Liu, Q., Wang, S., & Cui, D. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109202 · Cited by 41
Batyrova, B., Luwaert, F., Maravelia, P., Miyabayashi, Y., Vashist, N., Stark, J. M., Soori, S. Y., Tibbitt, C. A., Riese, P., Coquet, J. M., et al. (2019) · Immunity Inflammation and Disease · doi:10.1002/iid3.279 · Cited by 38
Cellular Senescence in Immunity against Infections
Marrella, V., Facoetti, A., & Cassani, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911845 · Cited by 38
“Moreover, senescent CD4 T cells expressing PD-1 and CD153 have been shown to accumulate in the spleens of aged mice [32].”
BackgroundNutrition and cellular senescence in obesity-related disorders
Rubio‐Tomás, T., Rueda‐Robles, A., Plaza‐Díaz, J., & Álvarez‐Mercado, A. I. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108861 · Cited by 40
Implications of inflammatory states on dysfunctional immune responses in aging and obesity
Thomas, A. L., Alarcon, P. C., Divanovic, S., Chougnet, C. A., Hildeman, D. A., & Moreno-Fernandez, M. E. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.732414 · Cited by 35
“The immune system in obesity has been posited to display an “immunosenescence” phenotype, similar to that seen in aging (Shirakawa et al., 2016; Salvestrini et al., 2019), where cells become more broadly inflammatory even though their cellspecific functionality is altered.”
BackgroundSawaki, D., Zhang, Y., Mohamadi, A., Pini, M., Mezdari, Z., Lipskaia, L., Naushad, S., Lamendour, L., Altintas, D. M., Breau, M., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.145811 · Cited by 36
“OPN is a matricellular protein involved in intracellular and extracellular signaling mediating cell-to-cell interactions, immune cell function, inflammation, and tissue remodeling (20, 21).”
BackgroundSim, B. C., Kang, Y. E., You, S. K., Lee, S. E., Nga, H. T., Lee, H. Y., Nguyen, T. L., Moon, J. S., Tian, J., Jang, H. J., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06146-8 · Cited by 35
“Senescent T-cell-mediated inflammatory responses are associated with the pathogenesis of acute coronary syndrome and hypertension [7, 8], and T-cell senescence is also linked to obesity and type 2 diabetes (T2D) in humans and mice [9, 10].”
Shirakawa, K., Endo, J., Katsumata, Y., Yamamoto, T., Kataoka, M., Isobe, S., Yoshida, N., Fukuda, K., & Sano, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186303 · Cited by 34
Self-citationCellular senescence and senescence‐associated T cells as a potential therapeutic target
Nakagami, H. (2019) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13851 · Cited by 34
Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy
Kuehm, L. M., Khojandi, N., Piening, A., Klevorn, L. E., Geraud, S. C., McLaughlin, N. R., Griffett, K., Burris, T. P., Pyles, K. D., Nelson, A. M., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0396 · Cited by 35
“Immune defects associated with obesity have been described by others, but the variety of proposed mechanisms and conflicting data have unfortunately not produced a consensus (10, 17, 23, 52, 53).”
BackgroundAdipose tissue in older individuals: a contributing factor to sarcopenia
Wang, T., Zhou, D., & Hong, Z. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155998 · Cited by 37
Osteopontin - The stirring multifunctional regulatory factor in multisystem aging
Du, Y., Mao, L., Wang, Z., Yan, K., Zhang, L., & Zou, J. T. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1014853 · Cited by 34
“The CD153+PD-1+CD44hiCD4+ T cells produced by visceral fat secrete large amounts of OPN and PD-1 resistance, leading to inflammation and promoting aging (104).”
BackgroundDrastic transformation of visceral adipose tissue and peripheral CD4 T cells in obesity
Shirakawa, K., & Sano, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1044737 · Cited by 35
“function and causes VAT inflammation (7).”
BackgroundInfluentialSelf-citationTargeting senescent cells for the treatment of age-associated diseases
Suda, M., Tchkonia, T., Kirkland, J. L., & Minamino, T. (2024) · The Journal of Biochemistry · doi:10.1093/jb/mvae091 · Cited by 38
Jiang, J., Yang, M., Zhu, H., Long, D., He, Z., Liu, J., He, L., Tan, Y., Akbar, A. N., Reddy, V. R., et al. (2024) · European Journal of Immunology · doi:10.1002/eji.202350603 · Cited by 31
“…level of CD4 + CD44 hi CD62L − PD-1 + CD153 + senescent CD4 + T cells has been detected in the germination center (GC) of the (NZB × NZW) F1 lupus model, suggesting their contribution to the pathogenesis of lupus erythematosus through promoting the production of autoantibodies such as ANA [20, 21].”
BackgroundA nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 33
Vick, L. V., Canter, R. J., Monjazeb, A. M., & Murphy, W. J. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.07.004 · Cited by 35
Obesity as an immune-modifying factor in cancer immunotherapy
Canter, R. J., Le, C. T., Beerthuijzen, J. M. T., & Murphy, W. J. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ri1017-401rr · Cited by 30
Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction
Yamamoto, T., Endo, J., Kataoka, M., Matsuhashi, T., Katsumata, Y., Shirakawa, K., Yoshida, N., Isobe, S., Moriyama, H., Goto, S., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208396 · Cited by 30
Self-citationSaigusa, R., Vallejo, J., Gulati, R., Suthahar, S. S. A., Suryawanshi, V., Alimadadi, A., Makings, J., Durant, C. P., Freuchet, A., Roy, P., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179875 · Cited by 26
Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy
Pasquarelli-do-Nascimento, G., Machado, S. A., de Carvalho, J. M. A., & Magalhães, K. G. (2022) · Immunotherapy Advances · doi:10.1093/immadv/ltac015 · Cited by 29
“M1 macrophages make up over 50% of WATs’ immune cells in individuals with obesity.”
BackgroundKornicka, K., Śmieszek, A., Węgrzyn, A., Röcken, M., & Marycz, K. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7110383 · Cited by 28
“[22] demonstrated elevated levels of activated CD4 T cells in the visceral adipose tissue of obese mice.”
BackgroundThe impact of body mass index on adaptive immune cells in the human bone marrow
Pangrazzi, L., Naismith, E., Miggitsch, C., Arana, J. A. C., Keller, M., Grubeck‐Loebenstein, B., & Weinberger, B. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00186-w · Cited by 28
“Despite this, although a link between obesity and T cell senescence has been suggested in murine adipose tissue [38], only few senescent-like populations were influenced by body weight in our cohort, in both BM and PB.”
BackgroundCallender, L. A., Carroll, E. C., Garrod-Ketchley, C., Schroth, J., Byström, J., Berryman, V., Pattrick, M., Campbell-Richards, D., Hood, G., Hitman, G. A., et al. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.681428 · Cited by 30
“, 2016), obesity (Shirakawa et al., 2016) and rheumatoid arthritis (Weyand et al.”
BackgroundResultZhang, H., Fan, Q., Xie, H., Lu, L., Tao, R., Wang, F., Xi, R., Hu, J., Chen, Q., Shen, W., et al. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00360 · Cited by 27
Self-citationLymphocytes upregulate CD36 in adipose tissue and liver
Couturier, J. P., Nuotio-Antar, A. M., Agarwal, N., Wilkerson, G. K., Saha, P., Kulkarni, V., Lakhashe, S. K., Esquivel, J., Nehete, P. N., Ruprecht, R. M., et al. (2019) · Adipocyte · doi:10.1080/21623945.2019.1609202 · Cited by 26
T lymphocyte depletion ameliorates age-related metabolic impairments in mice
Trott, D. W., Islam, M. T., Buckley, D. J., Donato, A. J., Dutson, T., Sorensen, E. S., Cai, J., Gogulamudi, V. R., Phuong, T. T. T., & Lesniewski, L. A. (2021) · GeroScience · doi:10.1007/s11357-021-00368-4 · Cited by 27
“This observation combined with the role of effector memory cells in diet-induced metabolic dysfunction [18, 32] suggests that effector memory cells may play a key role in age-related visceral adipose inflammation.”
BackgroundFukushima, Y., Sakamoto, K., Matsuda, M., Yoshikai, Y., Yagita∥, H., Kitamura, D., Chihara, M., Minato, N., & Hattori, M. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111373 · Cited by 28
Self-citationArata, Y., Watanabe, A., Motosugi, R., Murakami, R., Goto, T., Hori, S., Hirayama, S., Hamazaki, J., & Murata, S. (2019) · Genes to Cells · doi:10.1111/gtc.12728 · Cited by 25
Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade
Alden, S. L., Charmsaz, S., Li, H. L., Tsai, H., Danilova, L., Munjal, K., Brancati, M., Warner, A., Howe, K., Griffin, E., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009734 · Cited by 29
Yan, X., Imano, N., Tamaki, K., Sano, M., & Shinmura, K. (2021) · PLoS ONE · doi:10.1371/journal.pone.0252547 · Cited by 27
“Thus, SA-T cells are potential therapeutic targets for senolysis [8, 10].”
BackgroundMethodResultInfluentialSelf-citationA new clinical age of aging research
Zhang, Z., Yang, R., Zi, Z., & Liu, B. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.08.004 · Cited by 25
“CD153, also known as tumor necrosis factor (TNF) superfamily member 8, was identi fi ed as a surface marker capable of de fi ning a subset of senescent T cells that accumulated in the visceral adipose tissues of high-fat diet-induced obese mice [36,37].”
Human Adipose Tissue Metabolism in Obesity
Lin, S., & Jensen, M. D. (2025) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes25025 · Cited by 25
“76,85 In murine models, over-nutrition and obesity lead to an accumulation of oxidative stresses, increased markers of cellular senescence (p53 and senescence-associated β -galactosidase), and an increase in proinflammatory macrophages in adipose tissue.”
Kurosawa, M., Shikama, Y., Furukawa, M., Arakaki, R., Ishimaru, N., & Matsushita, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052302 · Cited by 23
“Accumulating evidence indicates that SA-Ts are involved in the pathogenesis of many diseases, such as an autoimmune disease [16] and metabolic disorders [15].”
BackgroundSenescence and Type 2 Diabetic Cardiomyopathy: How Young Can You Die of Old Age?
Henson, S. M., & Aksentijević, D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.716517 · Cited by 23
“There is an ever-growing appreciation that senescent T cells also play a role in many chronic inflammatory and metabolic diseases (Shirakawa et al., 2016; Callender et al., 2018).”
BackgroundImmunometabolic Dysregulation at the Intersection of Obesity and COVID-19
Khwatenge, C. N., Pate, M., Miller, L. C., & Sang, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.732913 · Cited by 22
Rühle, A., Todorović, J., Spohn, S. K. B., Gkika, E., Becker, C., Knopf, A., Zamboglou, C., Sprave, T., Werner, M., Grosu, A., et al. (2022) · Radiation Oncology · doi:10.1186/s13014-022-02153-9 · Cited by 24
“While plasma levels of osteopontin, a bone sialoprotein, have shown to exhibit predictive value regarding tumor hypoxia and the potential benefit of the hypoxia modifier nimorazole [44, 45], osteopontin was also found to be abundantly secreted by immunosenescent T cells [46, 47].”
BackgroundKato, A., Takaori‐Kondo, A., Minato, N., & Hamazaki, Y. (2018) · European Journal of Immunology · doi:10.1002/eji.201747431 · Cited by 23
Self-citationObesity, Senescence, and Senolytics
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2021) · Handbook of Experimental Pharmacology · doi:10.1007/164_2021_555 · Cited by 22
Zhou, Z., Zhang, H., Tao, Y., Jie, H., Zhao, J., Zang, J., Li, H., Wang, Y., Wang, T., Zhao, H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112424 · Cited by 24
Involvement of adiponectin in age-related increases in tear production in mice
Shikama, Y., Kurosawa, M., Furukawa, M., Ishimaru, N., & Matsushita, K. (2019) · Aging · doi:10.18632/aging.102322 · Cited by 22
PD-1 Blockade Reverses Obesity-Mediated T Cell Priming Impairment
Le, C. T., Khuat, L. T., Caryotakis, S. E., Wang, M., Dunai, C., Nguyen, A. V., Vick, L. V., Stoffel, K. M., Blazar, B. R., Monjazeb, A. M., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.590568 · Cited by 19
“In DIO mice, CD4+ T cells display increased senescence phenotypes with compromised proliferation, reduced IFN-g production, and upregulation of PD-1 in visceral fat (26).”
BackgroundRepurposing digoxin for geroprotection in patients with frailty and multimorbidity
Lee, H., Wilson, D. V., Bunting, K. V., Kotecha, D., & Jackson, T. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101860 · Cited by 19
“Digoxin treatment for three weeks duration in mouse models of Alzheimer’s disease reduced brain TNF-α levels after a (Erdogan et al., 2022).”
BackgroundInfluentialImmunometabolism in type 2 diabetes mellitus: tissue-specific interactions
Pinheiro-Machado, E., Gurgul-Convey, E., & Marzec, M. (2020) · Archives of Medical Science · doi:10.5114/aoms.2020.92674 · Cited by 19
“It was demonstrated that activated CD4+ T cells (CD4+CD44 hi CD62L lo ) accumulate in the visceral AT of obese mice and display features of cellular senescence [81].”
BackgroundRocha-Rodrigues, S., Matos, A., Afonso, J., Mendes-Ferreira, M., Abade, E., Teixeira, E., Silva, B., Murawska-Ciałowicz, E., Oliveira, M. J., & Ribeiro, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094469 · Cited by 17
Xu, Y., Wang, Z., Li, S., Su, J., Gao, L., Ou, J., Lin, Z., Luo, O. J., Xiao, C., & Chen, G. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2695-x · Cited by 20
“Furthermore, obesity accelerates T-cell aging in the visceral adipose tissue of mice (Shirakawa et al., 2016), as evidenced by the accumulation of CD153 + PD-1 + CD44 + CD4 + T cells in obese mice, resembling the phenotype of age-related T cells (Shirakawa et al., 2016).”
Félix‐Soriano, E., Sáinź, N., Fernández‐Galilea, M., Gil‐Iturbe, E., Celay, J., Martinez-Climent, J. A., & Moreno-Aliaga, M. J. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109153 · Cited by 18
A Role of Sodium-Glucose Co-Transporter 2 in Cardiorenal Anemia Iron Deficiency Syndrome
Sano, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065983 · Cited by 16
Self-citationRecent Advances in Senolysis for Age-Related Diseases
Aratani, S., & Nakanishi, M. (2023) · Physiology · doi:10.1152/physiol.00003.2023 · Cited by 16
Label-free optical metabolic imaging of adipose tissues for prediabetes diagnosis
Chen, L., Qin, G., Liu, Y., Li, M., Li, Y., Guo, L., Du, L., Zheng, W., Wu, P., Chuang, Y.-H., et al. (2023) · Theranostics · doi:10.7150/thno.82697 · Cited by 17
“Obesity and diabetic microenvironment could trigger inflammaging and immunosenescence [62, 63], which may cause more lipofuscin deposition in macrophages.”
BackgroundThe PD-1/PD-L1 Axis in the Biology of MASLD
Pipitone, R. M., Lupo, G., Zito, R., Javed, A., Petta, S., Pennisi, G., & Grimaudo, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073671 · Cited by 20
“Shirakawa and colleagues demonstrated that in obese WATs, there is a unique subpopulation of CD153 + , PD-1 + , CD44hi, CD4 + , and T lymphocytes that is linked with WAT inflammation and systemic insulin resistance [112].”
Divergent mechanisms of metabolic dysfunction drive fibroblast and T-cell senescence
Callender, L. A., Carroll, E. C., Bober, E. A., & Henson, S. M. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.06.001 · Cited by 17
“2016), obesity (Shirakawa et al., 2016) and rheumatoid arthritis (Weyand et al.”
Boßlau, T. K., Wasserfurth, P., Krüger, B., Reichel, T., Palmowski, J., Nebl, J., Weyh, C., Schenk, A., Joisten, N., Stahl, F., et al. (2021) · Cells · doi:10.3390/cells10050998 · Cited by 16
“In parallel, the expansion of visceral adipose tissue accelerates T cell differentiation by the progressive release of pro-inflammatory adipokines and cytokines [30].”
BackgroundImano, N., Shojima, K., Tamaki, K., & Shinmura, K. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00469.2022 · Cited by 16
Self-citationThe Role of Adaptive Immunity in Diabetic Retinopathy
Xue, M., Mao, X., Chen, M., Yin, W., Yuan, S., & Liu, Q. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11216499 · Cited by 16
“demonstrated that activated CD4+ T cells increased in the visceral adipose tissue of obese mice [25].”
BackgroundSystemic immunometabolism and responses to vaccines: insights from T and B cell perspectives
Nettelfield, S., Yu, D., & Cañete, P. F. (2023) · International Immunology · doi:10.1093/intimm/dxad021 · Cited by 15
“Moreover, following influenza infection, obese individuals exhibit reduced numbers of memory T cells accompanied by abnormal metabolic signatures, mirrored by an increase in visceral adipose tissue resident T cell senescence (65, 66).”
BackgroundMyeloid-Derived Suppressor Cells (MDSCs) and Obesity-Induced Inflammation in Type 2 Diabetes
Ghemiș, L., Goriuc, A., Minea, B., Botnariu, G., Mârțu, M.-A., Ențuc, M., Cioloca, D. P., & Foia, L. G. (2024) · Diagnostics · doi:10.3390/diagnostics14212453 · Cited by 15
Adipose Tissue T Cells in HIV/SIV Infection
Wanjalla, C. N., McDonnell, W. J., & Koethe, J. R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02730 · Cited by 16
“A fraction of the PD-1 CD44hi CD4 T cells also expressed CD153 (CD30L), a type II membrane glycoprotein that is present primarily on activated CD4 T cells, and the CD153 PD-1 CD44hi CD4 T cells were found to express genes linked to senescence (38).”
BackgroundPEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation
Pezhman, L., Hopkin, S. J., Begum, J., Heising, S., Nasteska, D., Wahid, M., Rainger, G. E., Hodson, D. J., Iqbal, A. J., Chimen, M., et al. (2023) · Clinical & Experimental Immunology · doi:10.1093/cei/uxad022 · Cited by 14
Soysouvanh, F., Rousseau, D., Bonnafous, S., Bourinet, M., Strazzulla, A., Patouraux, S., Machowiak, J., Farrugia, M. A., Iannelli, A., Tran, A., et al. (2023) · Obesity · doi:10.1002/oby.23868 · Cited by 14
“These T cells possess characteristics of cellular senescence [42].”
BackgroundSenescent T Cells in Age-Related Diseases
Yu, P.-J., Zhou, M. L., Liu, Y., & Du, J. (2024) · Aging and Disease · doi:10.14336/ad.2024.0219 · Cited by 16
Miftahussurur, M., Yuliyanasari, N., Rejeki, P. S., Hidayati, H. B., & Subsomwong, P. (2024) · Journal of Medicine and Life · doi:10.25122/jml-2023-0370 · Cited by 18
Otoda, T., Aihara, K., & Takayama, T. (2025) · Biomedicines · doi:10.3390/biomedicines13051053 · Cited by 14
Pro-tumorigenic role of type 2 diabetes-induced cellular senescence in colorectal cancer
Melia, F., Udomjarumanee, P., Zinovkin, D. A., Arghiani, N., & Pranjol, M. Z. I. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.975644 · Cited by 14
Zhou, Z., Zhang, H., Tao, Y., Zang, J., Zhao, J., Li, H., Wang, Y., Wang, T., Zhao, H., Wang, F., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102877 · Cited by 13
Senescence-associated T cells in immunosenescence and diseases
Fukushima, Y., Ueno, R., Minato, N., & Hattori, M. (2024) · International Immunology · doi:10.1093/intimm/dxae056 · Cited by 14
Self-citationThiagarajan, D., Quadri, N., Jawahar, S., Zirpoli, H., del Pozo, C. H., López‐Díez, R., Hasan, S. N., Yepuri, G., Gugger, P. F., Finlin, B. S., et al. (2022) · Obesity · doi:10.1002/oby.23496 · Cited by 13
Shi, H., Xiao, M., Li, Y., Liu, X., Na, J., Liang, C., Hua, J., Meng, Q., Wei, M., Wang, W., et al. (2025) · Theranostics · doi:10.7150/thno.112633 · Cited by 12
“Accurate discrimination between senescent and exhausted T ‐ cell phenotypes is essential, as both states are marked by functional impairment and co-express inhibitory receptors such as PD 1 and CTLA 4 [179, 180].”
Vita, E., Stefani, A., Piro, G., Mastrantoni, L., Cintoni, M., Cicchetti, G., Sparagna, I., Monaca, F., Horn, G., Russo, J., et al. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03533-0 · Cited by 12
Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases
Yoshikawa, T., & Yanagita, M. (2025) · International Immunology · doi:10.1093/intimm/dxaf017 · Cited by 14
Network Pharmacology Study to Interpret Signaling Pathways of Ilex cornuta Leaves against Obesity
Oh, K., Adnan, M., & Cho, D. H. (2021) · Processes · doi:10.3390/pr9071106 · Cited by 12
“T cell receptor signaling pathway: T cell damage is accelerated by obesity; accordingly, T cell dysfunction is detrimental to maintain the immune system [50,51].”
BackgroundComplexity of Inflammation in the Trajectory of Vascular Disease: Interleukin 6 and Beyond
Sano, M. (2023) · Annals of Vascular Diseases · doi:10.3400/avd.ra.23-00003 · Cited by 11
Self-citationObesity is associated with a higher Torque Teno viral load compared to leanness
Herz, C. T., Kulterer, O. C., Kulifaj, D., Gelas, F., Franzke, B., Haupenthal, F., Prager, G., Langer, F. B., Marculescu, R., Haug, A. R., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.962090 · Cited by 11
“In a murine study, a high fat diet increased the proportion of T cells in the visceral adipose tissue, which were reminiscent of the senescence-associated CD4+ cells observed with human ageing (40).”
BackgroundGalvin, K. C., Conroy, M. J., Doyle, S. L., Dunne, M. R., Fahey, R., Foley, E., O’Sullivan, K. E., Doherty, D. G., Geoghegan, J., Ravi, N., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.01.039 · Cited by 11
Links between Immunologic Memory and Metabolic Cycling
Cottam, M. A., Itani, H. A., Beasley, A. A., & Hasty, A. H. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701713 · Cited by 13
Yang, X., Xiong, T., Dong, N., Wang, T., Zhong, H., Tang, S., Mao, Y., Zhu, G., & Wang, D. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115132 · Cited by 11
Autophagy of naïve CD4+T cells in aging – the role of body adiposity and physical fitness
Padilha, C. S., Kushkestani, M., Baptista, L. C. P., Krüger, K., & Lira, F. S. (2023) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2023.2 · Cited by 9
Early life thymectomy induces arterial dysfunction in mice
Buckley, D. J., Sharma, S., Joseph, B., Fayyaz, A. H., Canizales, A., Terrebonne, K. J., & Trott, D. W. (2023) · GeroScience · doi:10.1007/s11357-023-00853-y · Cited by 9
“CD4 + PD-1 + cells also been shown to contribute to adipose inflammation in high fat fed mice [39].”
Mohammed, H., & Salloom, D. F. (2020) · Meta Gene · doi:10.1016/j.mgene.2020.100845 · Cited by 9
Meng, D., Zhang, B., Wang, Y., Zheng, T., Hu, R., Wang, B., Otsu, K., Wang, Y., & Huang, G. (2022) · Diabetes · doi:10.2337/db21-0653 · Cited by 9
A Brief Introduction into the Renin-Angiotensin-Aldosterone System: New and Old Techniques
Thatcher, S. E. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7030-8_1 · Cited by 9
Interactions Between the Neuroendocrine System and T Lymphocytes in Diabetes
Andreone, L., Gimeno, M. L., & Perone, M. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00229 · Cited by 9
“This osteopontin-expressing T cells linked visceral adiposity with immune aging (110).”
BackgroundLi, Y., Li, X., Xue, Q., Wang, J., & Tan, J. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111404 · Cited by 9
Obesity, bone marrow adiposity, and leukemia: Time to act
Kumar, V., & Stewart, J. H. (2023) · Obesity Reviews · doi:10.1111/obr.13674 · Cited by 8
High-fat diet blunts T-cell responsiveness in Nile tilapia
Li, K., Zhu, J., Li, K., Liang, W., Zhang, J., Zhang, Q., Jiao, X., Wang, X., Wei, X., & Yang, J. (2022) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2022.104495 · Cited by 7
Brunelli, D. T., Bonfante, I. L. P., Boldrini, V. D. O., Scolfaro, P. G., Duft, R. G., Mateus, K. C. D. S., Fatori, R. F., Chacon‐Mikahil, M. P. T., Farias, A. S., Teixeira, A. M., et al. (2024) · Research Quarterly for Exercise and Sport · doi:10.1080/02701367.2023.2299716 · Cited by 7
“…cells, lymphocyte proliferation and chemotaxis of macrophages and lymphocytes (Hunsche et al., 2016), accelerate cellular senescence in T cells (Shirakawa et al., 2016), decrease production of naïve T cells (Yang et al., 2009), and impair B cell function by inducing differentiation of…”
Obesity-associated Inflammation and Alloimmunity
Zhou, H., Gizlenci, M., Xiao, Y., Martin, F., Nakamori, K., Zicari, E. M., Sato, Y., & Tullius, S. G. (2024) · Transplantation · doi:10.1097/tp.0000000000005183 · Cited by 8
“83 Additionally, in an experimental model of obesity-induced metabolic dysfunction, clearance of senescent cells improved metabolic functions.”
Siqueira, J. S., Palacio, T. L. N., Vieira, T. A., Nakandakare-Maia, E. T., Grandini, N. A., Ferron, A. J. T., Francisqueti‐Ferron, F. V., & Corrêa, C. R. (2023) · Nutrire · doi:10.1186/s41110-023-00206-x · Cited by 8
Giovenzana, A., Bezzecchi, E., Bichisecchi, A., Cardellini, S., Ragogna, F., Pedica, F., Invernizzi, F., di Filippo, L., Tomajer, V., Aleotti, F., et al. (2024) · iScience · doi:10.1016/j.isci.2024.109032 · Cited by 7
“12 16 Notably, CD4 T cells are resistant to cytokine-mediated suppression 13 and have a restricted T cell receptor (TCR) repertoire.”
BackgroundShirakawa, K., Yano, W., Inoue, K., Katsumata, Y., Endo, J., & Sano, M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0211387 · Cited by 7
Self-citationPalmer, A. K., Jensen, M. D., Tchkonia, T., & Kirkland, J. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822514-1.00009-2 · Cited by 7
A maternal high-fat diet may accelerate adipo-immunologic aging in offspring
Imai, A., Fujimoto, E., Tamura, K., Utsuyama, M., & Sato, K. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.01.008 · Cited by 7
The immune duality of osteopontin and its therapeutic implications for kidney transplantation
Leung, J., Qu, L., Ye, Q., & Zhong, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1520777 · Cited by 6
Lin, C., Yang, J., Su, H., Zhang, X., & Wang, B. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s514521 · Cited by 7
“145 These findings suggest a mutually reinforcing relationship between immune cell senescence and obesity.”
The role of thymic epithelium in thymus development and age-related thymic involution
Fujimori, S., & Ohigashi, I. (2024) · The Journal of Medical Investigation · doi:10.2152/jmi.71.29 · Cited by 6
Broadway, R., Patel, N. M., Hillier, L. E., El-briri, A., Korneva, Y. S., Zinovkin, D. A., & Pranjol, M. Z. I. (2021) · Life · doi:10.3390/life11080788 · Cited by 5
Regulation of STUB1 expression and its biological significance in mouse Sertoli cells
Li, T., Zheng, C., Han, W.-J., & Chen, Z. (2022) · Systems Biology in Reproductive Medicine · doi:10.1080/19396368.2022.2027554 · Cited by 6
“It is generally accepted that cell senescence is tightly linked to abnormal lipid accumulation (Shirakawa et al. 2016; Liu X et al. 2021).”
Background
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 ›
Are you an author, or do you see a problem with this page? Request a review
