{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:53:57Z","timestamp":1793796837420,"version":"4.6.1"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI108891,R01AG045779,R01AI129191,U19AI057266,R01AR042527,R01HL117913,R01AI108906,R01HL142068"],"award-info":[{"award-number":["R01AI108891,R01AG045779,R01AI129191,U19AI057266,R01AR042527,R01HL117913,R01AI108906,R01HL142068"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,8]]},"abstract":"<jats:p>\n                    The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell compartment into older age. Here, we describe that naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.172848","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T19:14:35Z","timestamp":1707851675000},"source":"Crossref","is-referenced-by-count":10,"title":["PREX1 improves homeostatic proliferation to maintain a naive CD4+ T cell compartment in older age"],"prefix":"10.1172","volume":"9","author":[{"given":"Huimin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6019-6132","authenticated-orcid":true,"given":"Hirohisa","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of 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