{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:38:39Z","timestamp":1769215119329,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23K15135"],"award-info":[{"award-number":["23K15135"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T [T-reg] cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K\/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3fl\/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart.<\/jats:p>","DOI":"10.3390\/cells15020204","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T13:55:34Z","timestamp":1769176534000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal Regulatory T Cells Mediate Fibrosis and Contribute to Cardiac Repair"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-4358","authenticated-orcid":false,"given":"Tabito","family":"Kino","sequence":"first","affiliation":[{"name":"Department of Cardiology, Yokohama City University, Yokohama 236-0004, Japan"},{"name":"Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadia","family":"Mohsin","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Chiba","sequence":"additional","affiliation":[{"name":"Advanced Adult Nursing, Department of Nursing, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Ishigami","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Causes of Death Collaborators (2018). 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