{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:14:43Z","timestamp":1769123683035,"version":"3.49.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Age-related immunosenescence is characterized by progressive dysfunction of adaptive immune response and increased autoimmunity. Nevertheless, the impact of aging on CD4+ regulatory T cells that are master regulators of the immune system remains largely unclear. Here, we report cellular and molecular hallmarks of regulatory T cells derived from murine lymphoid and adipose tissues at 3, 18, and 24 mo of age, respectively, by analyzing their heterogeneity that displays dynamic changes in transcriptomic effector signatures at a single-cell resolution. Although the proportion of regulatory T cells among total Cd4+ T cells, as well as their expression levels of Foxp3, did not show any global change with time, we have identified 6 transcriptomically distinct clusters of regulatory T cells with cross-tissue conserved hallmarks of aging, including increased numbers of proinflammatory regulatory T cells, reduced precursor cells, increased immature and mature T follicular regulatory cells potentially supported by a metabolic switch from oxidative phosphorylation to glycolysis, a gradual loss of CD150hi regulatory T cells that support hematopoiesis, and increased adipose tissue-specific regulatory T cells that are associated with metabolic disease. To dissect the impact of immunosenescence on humoral immunity, we propose some potential mechanisms underlying T follicular regulatory cell\u2013mediated dysfunction by interactome analysis on T follicular regulatory cells, T follicular helper cells, and B cells during aging. Lastly, spatiotemporal analysis further revealed trajectories of regulatory T-cell aging that demonstrate the most significant changes in marrow and adipose tissues that might contribute to the development of age-related immunosenescence and type 2 diabetes. Taken together, our findings could provide a better understanding of age-associated regulatory T-cell heterogeneity in lymphoid and adipose tissues, as well as regulatory T-cell hallmarks during progressive adaptation to aging that could be therapeutically targeted for rejuvenating the aging immune system in the future.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad104","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:32:42Z","timestamp":1694079162000},"page":"19-35","source":"Crossref","is-referenced-by-count":14,"title":["Single-cell transcriptomics of Treg reveals hallmarks and trajectories of immunological aging"],"prefix":"10.1093","volume":"115","author":[{"given":"Kevin Y","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong , 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China"},{"name":"Division of Cardiology, Queen Mary Hospital, The University of Hong Kong , 102 Pok Fu Lam Road, Hong Kong, China"}]},{"given":"Jinyue","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong , 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China"}]},{"given":"Zhangjing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong , 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China"}]},{"given":"Hung Fat","family":"Tse","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Queen Mary Hospital, The University of Hong Kong , 102 Pok Fu Lam Road, Hong Kong, China"}]},{"given":"Liwei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Mary Hospital, The University of Hong Kong , 102 Pok Fu Lam Road, Hong Kong, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-8500","authenticated-orcid":false,"given":"Luis","family":"Graca","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Edif\u00edcio Egas Moniz, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"given":"Kathy O","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong , 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China"},{"name":"Li Ka Shing Institute of Health Science, Prince of Wales Hospital, The Chinese University of Hong Kong , 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China"},{"name":"Shenzhen Research Institute, The Chinese University of Hong Kong , No. 10 2nd Yuexin Road, Nanshan District, Shenzhen, China"}]}],"member":"286","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"issue":"3","key":"2024010518212379800_qiad104-B1","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1172\/JCI64096","article-title":"Causes, consequences, and reversal of immune system aging","volume":"123","author":"Montecino-Rodriguez","year":"2013","journal-title":"J Clin Invest"},{"key":"2024010518212379800_qiad104-B2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3389\/fimmu.2019.00318","article-title":"B cell dysfunction associated with aging and autoimmune diseases","volume":"10","author":"Ma","year":"2019","journal-title":"Front Immunol"},{"issue":"2","key":"2024010518212379800_qiad104-B3","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000355303","article-title":"Regulatory T cells and the immune aging process: a 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