{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:14:23Z","timestamp":1792066463640,"version":"4.4.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Type 2 diabetes mellitus (T2D) is characterized by chronic, low-grade inflammation and immune dysregulation, contributing to insulin resistance and metabolic complications. Regulatory T cells (Tregs) are key modulators of immune homeostasis, and their therapeutic expansion has shown promise in limiting inflammation. Here, we investigated whether\n                      <jats:italic>in vivo<\/jats:italic>\n                      Treg expansion could modulate metabolic and inflammatory responses in T2D in a sex-specific manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female db\/db and db\/+ mice received intraperitoneal injections of IL-2\/anti-IL-2 (JES6-1) complexes for six weeks to induce endogenous Treg expansion. Body weight, blood glucose, and insulin levels were monitored to calculate HOMA-IR. Plasma inflammatory and anti-inflammatory mediators (CRP, adiponectin, IL-10, IL-13, CCL3) were quantified by bead-based immunoassays. Hepatic triglycerides and gene expression of Foxp3, F4\/80, Ppar\u03b3, Il10 and Il13 were analyzed by biochemical assays, western blot, and RT-qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treg expansion reduced weight gain in db\/db mice independently of food intake. Female mice displayed lower HOMA-IR, decreased CRP, and increased adiponectin, IL-10, and IL-13 levels, whereas males showed limited improvement. Hepatic triglycerides and F4\/80 expression were reduced after Treg expansion, with restored Foxp3 and elevated Il10\/Il13 expression, indicating diminished hepatic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Endogenous Treg expansion exerts sex-specific metabolic and anti-inflammatory benefits in db\/db T2D mice, with females showing greater improvements in insulin resistance, inflammation, and hepatic lipid metabolism. These findings support Treg-based immunomodulation as a potential therapeutic approach for T2D and emphasize the need for sex-specific considerations in future research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1599985","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:20:43Z","timestamp":1761546043000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex-specific metabolic effects of Treg expansion in db\/db mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Daniel","family":"P\u00e9rez-Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda 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