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While the role of costimulation in effector and memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell development is well characterized, how costimulatory signaling governs CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    cells homeostasis at the memory phase remains poorly defined. Here it is revealed that the costimulatory receptors CD27 and ICOS coordinately sustain PD\u20101\n                    <jats:sup>high<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD\u20101\/PD\u2010L1 blockade, thereby facilitating the rejuvenation of PD\u20101\n                    <jats:sup>high<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27\/ICOS, governing proliferative renewal and maintenance of PD\u20101\n                    <jats:sup>high<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    cells. Therapeutic administration of a CD27 agonist not only amplified this T\n                    <jats:sub>RM<\/jats:sub>\n                    cell subset in late\u2010stage memory but also conferred cross\u2010protective immunity against heterosubtypic viral challenges. Clinically, the expressions of CD27 and ICOS are enriched in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, these findings establish the \u201cCD27\/ICOS\u2010NR4A1\u2010proliferation\u201d axis as a linchpin of PD\u20101\/PD\u2010L1\u2010mediated T\n                    <jats:sub>RM<\/jats:sub>\n                    cell homeostasis, revealing druggable targets for intercepting infection\u2010associated fibrotic progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512452","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T08:41:41Z","timestamp":1763628101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CD27 and ICOS as Targets of PD\u20101\/PD\u2010L1 Signaling to Regulate Resident Memory CD8\n                    <sup>+<\/sup>\n                    T\u2010Cell\u2010Mediated Pulmonary Protection and Pathology"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuanyuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pulmonary 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