{"id":71856,"date":"2026-07-30T12:56:26","date_gmt":"2026-07-30T10:56:26","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/30\/lowering-cd40l-expression-in-murine-lupus-results-in-an-increase-in-disease-indicators-in-female-but-not-male-b6-mice\/"},"modified":"2026-07-30T12:56:26","modified_gmt":"2026-07-30T10:56:26","slug":"lowering-cd40l-expression-in-murine-lupus-results-in-an-increase-in-disease-indicators-in-female-but-not-male-b6-mice","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/30\/lowering-cd40l-expression-in-murine-lupus-results-in-an-increase-in-disease-indicators-in-female-but-not-male-b6-mice\/","title":{"rendered":"Lowering CD40L expression in murine lupus results in an increase in disease indicators in female but not male B6 mice"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Jul 10;215(7):vkag205. doi: 10.1093\/jimmun\/vkag205.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Our laboratory has previously described a mouse model (CD40L\u03945) that produces 60% of wild-type CD40L due to a targeted deletion in an RNA binding site within the CD40L message. The CD40L\u03945 mutation, which destabilizes CD40L mRNA during T-cell activation, causes disrupted germinal center (GC) formation, leading to reduced levels of memory B cells and switched antibodies. In this study, we used our model of limited CD40L expression to investigate its effect on systemic lupus erythematosus (SLE, or lupus) using 2 different mouse models of SLE. The first model used the hydrocarbon oil pristane to induce lupus-like symptoms over a 6-month period, and the second utilized a chronic graft-versus-host disease (bm12-cGVHD) that resembles lupus and allowed us to monitor the early events in disease development. Importantly, we found that in both systems, female mice expressing the CD40L\u03945 mutation showed a consistent increase in elevated antibody-secreting cells and autoantibody titers. In addition, pristane-induced lupus female CD40L\u03945 mice had higher levels of immunocomplex deposition in the kidney compared to all other cohorts. Increases in autoantibodies and GC cells in female CD40L\u03945 versus wild-type recipient mice were also evident in the bm12-cGVHD model. Additionally, CD4+ T cells from female CD40L\u03945 recipient mice were skewed toward a Th2 phenotype and expressed a distinct cytokine expression pattern upon activation of dendritic cells. Overall, our results support a nuanced role for optimal CD40L expression in lupus and suggest a sex-determined threshold of CD40L-CD40 signaling that is critical at the very early steps of disease progression.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42528416\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260730065626&amp;v=2.20.0.post5+40e1b98\">42528416<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag205\">10.1093\/jimmun\/vkag205<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Jul 10;215(7):vkag205. doi: 10.1093\/jimmun\/vkag205. ABSTRACT Our laboratory has previously described a mouse model (CD40L\u03945) that produces 60% of wild-type CD40L due to a targeted deletion in an RNA binding site within the CD40L message. The CD40L\u03945 mutation, which destabilizes CD40L mRNA during T-cell activation, causes disrupted germinal center (GC) formation, leading to &#8230; <a title=\"Lowering CD40L expression in murine lupus results in an increase in disease indicators in female but not male B6 mice\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/30\/lowering-cd40l-expression-in-murine-lupus-results-in-an-increase-in-disease-indicators-in-female-but-not-male-b6-mice\/\" aria-label=\"Read more about Lowering CD40L expression in murine lupus results in an increase in disease indicators in female but not male B6 mice\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-71856","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71856","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=71856"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71856\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=71856"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=71856"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=71856"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}