{"id":37656,"date":"2025-07-09T18:47:56","date_gmt":"2025-07-09T16:47:56","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/09\/macrophage-il-4-polarization-is-restricted-by-soluble-cd40-agonists-and-antigen-induced-cd154-but-not-by-constitutive-cd154-expressed-by-cd4-t-cellsmariana-suarez-martins-on-9-de-july-de-2\/"},"modified":"2025-07-09T18:47:56","modified_gmt":"2025-07-09T16:47:56","slug":"macrophage-il-4-polarization-is-restricted-by-soluble-cd40-agonists-and-antigen-induced-cd154-but-not-by-constitutive-cd154-expressed-by-cd4-t-cellsmariana-suarez-martins-on-9-de-july-de-2","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/09\/macrophage-il-4-polarization-is-restricted-by-soluble-cd40-agonists-and-antigen-induced-cd154-but-not-by-constitutive-cd154-expressed-by-cd4-t-cellsmariana-suarez-martins-on-9-de-july-de-2\/","title":{"rendered":"Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells\u200bMariana Su\u00e1rez-Martins   on 9 de July de 2025 at 10:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2025 Jul 9;117(7):qiaf069. doi: 10.1093\/jleuko\/qiaf069.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Stimulation of macrophages via CD40 promotes their classical activation. Therefore, CD154 (CD40 ligand) can be expected to oppose macrophage polarization and proliferation induced by IL-4. However, there are limited experimental data to support this, which is additionally complicated by the possibility of differential effects of CD40 agonists in different formats\/contexts. Whereas canonically CD4+ T cells upregulate CD154 strongly following exposure to cognate antigen, na\u00efve CD4+ cells constitutively express significant levels of CD154, which could be a tonic signal. Soluble CD154 and agonistic CD40 antibodies also trigger CD40 signaling. We explored these questions in a reductionist model of IL-4 delivery to mouse peritoneal cavity cells in vitro and in vivo. Soluble CD40 agonists inhibited M(IL-4) polarization, with a stronger effect on RELM-\u03b1 than on Ym1 (Chil3), as well as inhibiting IL-4-induced proliferation. CD154 provided by CD4+ cells in the context of an antigen-specific interaction blunted macrophage RELM-\u03b1 expression but did not affect Ym1. Macrophages negatively regulated, via CD40, constitutive cell-surface CD154 on na\u00efve CD4+ cells, both in vitro and in vivo. The large peritoneal macrophages of CD40 KO mice showed a moderately enhanced RELM-\u03b1 response to IL-4, but this was not a cell-autonomous effect. No differences between WT and CD40 KO mice were detected in IL-4-induced macrophage proliferation. We conclude that strong CD40 stimulation, including stimulation by CD154 expressed by antigen-specific CD4+ cells, blunts selected macrophage responses to IL-4, and that constitutive CD4+-cell CD154, in spite of interacting with CD40 on macrophages, does not directly influence macrophage responses to IL-4.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40631988\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20250709124754&amp;v=2.18.0.post9+e462414\">40631988<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiaf069\">10.1093\/jleuko\/qiaf069<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2025 Jul 9;117(7):qiaf069. doi: 10.1093\/jleuko\/qiaf069. ABSTRACT Stimulation of macrophages via CD40 promotes their classical activation. Therefore, CD154 (CD40 ligand) can be expected to oppose macrophage polarization and proliferation induced by IL-4. However, there are limited experimental data to support this, which is additionally complicated by the possibility of differential effects of CD40 &#8230; <a title=\"Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells\u200bMariana Su\u00e1rez-Martins   on 9 de July de 2025 at 10:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/07\/09\/macrophage-il-4-polarization-is-restricted-by-soluble-cd40-agonists-and-antigen-induced-cd154-but-not-by-constitutive-cd154-expressed-by-cd4-t-cellsmariana-suarez-martins-on-9-de-july-de-2\/\" aria-label=\"Read more about Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells\u200bMariana Su\u00e1rez-Martins   on 9 de July de 2025 at 10:00\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86,42],"tags":[],"class_list":["post-37656","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/37656","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=37656"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/37656\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=37656"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=37656"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=37656"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}