{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:47:15Z","timestamp":1790498835618,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T00:00:00Z","timestamp":1364342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Changes to innate cells, such as macrophages and myeloid\u2010derived suppressor cells (<jats:styled-content style=\"fixed-case\">MDSC<\/jats:styled-content>s), during aging in healthy or tumor\u2010bearing hosts are not well understood. We compared macrophage subpopulations and <jats:styled-content style=\"fixed-case\">MDSC<\/jats:styled-content>s from healthy young (6\u20138\u00a0weeks) C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice to those from healthy geriatric (24\u201328\u00a0months) mice. Spleens, lymph nodes, and bone marrow of geriatric hosts contained significantly more M2 macrophages and <jats:styled-content style=\"fixed-case\">MDSC<\/jats:styled-content>s than their younger counterparts. Peritoneal macrophages from geriatric, but not young, mice co\u2010expressed <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 and <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>1 that are usually mutually exclusively expressed by <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>2 macrophages. Nonetheless, macrophages from geriatric mice responded to <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>2 stimuli similarly to macrophages from young mice, although they secreted higher levels of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 in response to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104. We mimicked conditions that may occur within tumors by exposing macrophages from young vs. geriatric mice to mesothelioma or lung carcinoma tumor cell\u2013derived supernatants. While both supernatants skewed macrophages toward the <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>2\u2010phenotype regardless of age, only geriatric\u2010derived macrophages produced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, suggesting a more immunosuppressive tumor microenvironment will be established in the elderly. Both geriatric\u2010 and young\u2010derived macrophages induced allogeneic <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell proliferation, regardless of the stimuli used, including tumor supernatant. However, only macrophages from young mice induced <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 production. We examined the potential of an <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102\/agonist anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 antibody immunotherapy that eradicates large tumors in young hosts to activate macrophages from geriatric mice. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102\u2010\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40\u2010activated macrophages rescued <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell production of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 in geriatric mice. Therefore, targeting macrophages with <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102\/anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40 antibody may improve innate and <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell immunity in aging hosts.<\/jats:p>","DOI":"10.1111\/acel.12062","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T20:02:38Z","timestamp":1361908958000},"page":"345-357","source":"Crossref","is-referenced-by-count":154,"title":["Targeting macrophages rescues age\u2010related immune deficiencies in C57<scp>BL<\/scp>\/6J geriatric mice"],"prefix":"10.1111","volume":"12","author":[{"given":"Connie","family":"Jackaman","sequence":"first","affiliation":[{"name":"Immunology and Cancer Group School of Biomedical Sciences Curtin University Perth WA 6102 Australia"},{"name":"School of Biomedical Sciences CHIRI Biosciences Research Precinct Curtin University 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