{"id":61695,"date":"2026-04-15T20:51:25","date_gmt":"2026-04-15T18:51:25","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/15\/folate-receptor-beta-drives-nlrp3-inflammasome-activation-and-pyroptosis-in-macrophages-independent-of-folate-binding\/"},"modified":"2026-04-15T20:51:25","modified_gmt":"2026-04-15T18:51:25","slug":"folate-receptor-beta-drives-nlrp3-inflammasome-activation-and-pyroptosis-in-macrophages-independent-of-folate-binding","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/15\/folate-receptor-beta-drives-nlrp3-inflammasome-activation-and-pyroptosis-in-macrophages-independent-of-folate-binding\/","title":{"rendered":"Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Apr 15;215(4):vkag051. doi: 10.1093\/jimmun\/vkag051.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Folate receptor beta (FR\u03b2), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FR\u03b2 as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR\/Cas9-mediated gene deletion, we show that loss of FOLR2 severely impaired caspase-1 activation, gasdermin D cleavage, and IL-1\u03b2 release in response to multiple NLRP3 stimuli, without altering pro-IL-1\u03b2 induction. These defects were not rescued by exogenous folate and were independent of extracellular folate concentrations. Mechanistically, FOLR2\/FR\u03b2 appears to potentiate potassium efflux and the expression of multiple potassium channel-encoding genes. Single-cell RNA sequencing revealed broad transcriptional repression in FR\u03b2-deficient macrophages, including genes involved in inflammasome signaling and ion transport. Genome-wide methylation profiling showed increased CpG hypermethylation in FOLR2-deficient cells, consistent with reduced transcriptional activity. Our findings indicate that FR\u03b2 promotes NLRP3 activation in a folate-independent manner potentially by regulating DNA methylation, gene transcription, and K+ efflux in macrophages. These findings uncover a previously unrecognized immunoregulatory function for FR\u03b2, positioning it as a potential modulator of macrophage-driven inflammation in contexts such as host defense, autoimmunity, and tissue-specific immune responses at the tumor and maternal-fetal interface.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41984502\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260415145124&amp;v=2.19.0.post6+133c1fe\">41984502<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag051\">10.1093\/jimmun\/vkag051<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Apr 15;215(4):vkag051. doi: 10.1093\/jimmun\/vkag051. ABSTRACT Folate receptor beta (FR\u03b2), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FR\u03b2 as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR\/Cas9-mediated gene deletion, we &#8230; <a title=\"Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/04\/15\/folate-receptor-beta-drives-nlrp3-inflammasome-activation-and-pyroptosis-in-macrophages-independent-of-folate-binding\/\" aria-label=\"Read more about Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding\">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":[42,71],"tags":[],"class_list":["post-61695","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\/61695","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=61695"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/61695\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=61695"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=61695"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=61695"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}