{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:25:30Z","timestamp":1790871930258,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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:p>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells (Tregs) are essential for maintaining immune tolerance, and selective expansion of Tregs via TNFR2 signaling represents a promising therapeutic approach for autoimmune and inflammatory diseases. Here, we report the identification and characterization of UMR2-705, a novel TNFR2 agonist discovered through phage display screening.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , peptide UMR2\u2013705 selectively promoted Treg proliferation in both human peripheral blood mononuclear cells and murine CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell cultures without stimulating conventional CD4\n                    <jats:sup>+<\/jats:sup>\n                    effector or CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. This effect was abrogated by the TNFR2-specific blocking antibody TR75-54.7, indicating its TNFR2 dependency.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , administration of peptide UMR2\u2013705 expanded Tregs in murine spleen and lymph nodes, attenuated LPS-induced systemic cytokine release (IL-6, TNF-\u03b1, IL-17A) in serum, and preserved immune homeostasis during systemic inflammation through TNFR2-dependent modulation of the regulatory compartment. Transcriptomic profiling revealed activation of TNFR2-associated signaling and upregulation of immune-regulatory pathways. These findings identify peptide UMR2\u2013705 as a selective, peptide-based TNFR2 agonist with potent Treg-expanding and anti-inflammatory activities, supporting its potential as a therapeutic candidate for autoimmune and inflammatory disorders.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1696587","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:16:16Z","timestamp":1764134176000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel TNFR2 agonist peptide for the expansion of CD4+Foxp3+ regulatory T 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