{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:59:10Z","timestamp":1791493150203,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    CD28 expression is generally considered to be T lymphocyte specific. We have previously shown\n                    <jats:italic>CD28<\/jats:italic>\n                    mRNA expression in M\u2010CSF\u2010dependent anti\u2010inflammatory monocyte\u2010derived macrophages (M\u2010M\u00d8), and now demonstrate that CD28 cell surface expression is higher in M\u2010M\u00d8 than in GM\u2010CSF\u2010dependent macrophages, and that macrophage CD28 expression is regulated by MAFB and activin A. In vivo, CD28 was found in tumor\u2010associated macrophages and, to a lower extent, in pro\u2010inflammatory synovial fluid macrophages from rheumatoid arthritis patients. Analysis of mouse macrophages confirmed Cd28 expression in bone\u2010marrow derived M\u2010M\u00d8. Indeed, anti\u2010CD28 antibodies triggered ERK1\/2 phosphorylation in mouse M\u2010M\u00d8. At the functional level,\n                    <jats:italic>Cd28<\/jats:italic>\n                    KO M\u2010M\u00d8 exhibited a significantly higher capacity to activate the OVA\u2010specific proliferation of OT\u2010II CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells than WT M\u2010M\u00d8, as well as enhanced LPS\u2010induced IL\u20106 production. Besides, the\n                    <jats:italic>Cd28<\/jats:italic>\n                    KO M\u2010M\u00d8 transcriptome was significantly different from WT M\u2010M\u00d8 regarding the expression IFN response, inflammatory response, and TGF\u2010\u03b2 signaling related gene sets. Therefore, defective CD28 expression in mouse macrophages associates to changes in gene expression profile, what might contribute to the altered functionality displayed by\n                    <jats:italic>Cd28<\/jats:italic>\n                    KO M\u2010M\u00d8. Thus, CD28 expression appears as a hallmark of anti\u2010inflammatory macrophages and might be a target for immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048806","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T16:27:43Z","timestamp":1605025663000},"page":"824-834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["CD28 is expressed by macrophages with anti\u2010inflammatory potential and limits their T\u2010cell activating capacity"],"prefix":"10.1002","volume":"51","author":[{"given":"Lizbeth","family":"Estrada\u2010Capetillo","sequence":"first","affiliation":[{"name":"Unidad de InmunoMetabolismo e Inflamaci\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n Hospital General Universitario Gregorio Mara\u00f1\u00f3n Madrid 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