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Immunosenescence, the functional changes in immune cells with aging, impacts the age-associated immune response, but how immunosenescence and the molecular regulators of the age-associated immune response affect the clinical course of uveitis remains unclear. In the murine model of experimental autoimmune uveitis (EAU), aged mice demonstrated a delayed onset and peak of intraocular inflammation compared to young mice. In contrast to the canonical monophasic inflammation that rapidly resolves in young mice, aged mice developed persistent, chronic inflammation. Transcriptomic and flow-cytometric analyses of immune cells and the receptor-ligand interactome revealed a dominant macrophage-CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell signature. This signaling pathway was functionally altered on both ends: macrophages from aged mice had an impaired capacity to generate peripherally induced regulatory T cells (pTreg) through an IL-6 regulated pathway, while CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells co-cultured with aged macrophages demonstrated increased proliferation. Our study establishes aging as a key regulator of the effector immune response in uveitis. Regulatory T cells, specifically pTreg, are essential for resolving inflammation in uveitis and an impaired ability to induce pTreg led to a sustained, chronic inflammatory uveitis phenotype in old mice, thereby linking immunosenescence to persistent neuroinflammation. These findings highlight potential therapeutic avenues for vision-threatening uveitis, especially in older patients.\n                <\/jats:p>","DOI":"10.64898\/2026.01.15.697975","type":"posted-content","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:05:24Z","timestamp":1768910724000},"source":"Crossref","is-referenced-by-count":1,"title":["Macrophage immunosenescence prolongs intraocular inflammation in aged mice via impaired induction of regulatory T cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7375-8021","authenticated-orcid":false,"given":"Taku","family":"Yamamoto","sequence":"first","affiliation":[{"name":"John F. 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