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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The ovary is an immunologically dynamic tissue that coordinates recurrent inflammation-like remodeling while preserving local T cell tolerance, yet whether it actively instructs infiltrating lymphocyte phenotype or passively enriches pre-existing subsets has not been directly tested. To address this, we used peripheral double-negative T cells (DNTs; CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK1.1\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) as a coreceptor-null system to detect tissue-imposed phenotypic change after ovarian entry. Using adoptive transfer, labeled splenic DNTs accumulated in the ovary relative to other tissue sites, and donor DNTs acquired surface CD8 expression within 4 days of ovarian localization. Dissociated ovarian cells were sufficient to drive CD8 upregulation on sorted DNTs in vitro, supporting that ovarian cellular cues can promote this response. Ovarian single-cell RNA-seq provided supportive evidence for\n                    <jats:italic>Il7<\/jats:italic>\n                    -expressing stromal subsets, and an\n                    <jats:italic>Il7r<\/jats:italic>\n                    -enriched DNT-associated lymphoid population, findings compatible with local IL-7-associated microenvironmental cues that may contribute to conditioning infiltrating T cells. Functionally, IL-7R was required for efficient CD8 upregulation after ovarian localization, and IL-7R or IL-7 deficiency shifted the endogenous ovarian DNT: CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell balance. These findings support the ovary as an immune-conditioning environment in which tissue entry is associated with CD8 coreceptor induction on peripheral DNTs, and identify IL-7R signaling as a requirement for efficient induction in this setting.\n                  <\/jats:p>","DOI":"10.1007\/s00018-026-06295-x","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:25:28Z","timestamp":1781565928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ovarian localization drives IL-7R-dependent CD8 coreceptor expression in peripheral double-negative T cells"],"prefix":"10.1007","volume":"83","author":[{"given":"Toni","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-3177","authenticated-orcid":false,"given":"Enitome E.","family":"Bafor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"6295_CR1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1210\/er.2018-00075","volume":"40","author":"DM Duffy","year":"2019","unstructured":"Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE (2019) Ovulation: Parallels With Inflammatory Processes. 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