{"id":16917,"date":"2024-09-29T10:12:39","date_gmt":"2024-09-29T08:12:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/dissecting-the-metabolic-signaling-pathways-by-which-microbial-molecules-drive-the-differentiation-of-regulatory-b-cells-maik-luu\/"},"modified":"2024-09-29T10:12:39","modified_gmt":"2024-09-29T08:12:39","slug":"dissecting-the-metabolic-signaling-pathways-by-which-microbial-molecules-drive-the-differentiation-of-regulatory-b-cells-maik-luu","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/dissecting-the-metabolic-signaling-pathways-by-which-microbial-molecules-drive-the-differentiation-of-regulatory-b-cells-maik-luu\/","title":{"rendered":"Dissecting the metabolic signaling pathways by which microbial molecules drive the differentiation of regulatory B cells. Maik Luu"},"content":{"rendered":"<div>\n<p>Mucosal Immunol. 2024 Sep 16:S1933-0219(24)00096-5. doi: 10.1016\/j.mucimm.2024.09.003. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>The host-microbiome axis has been implicated in promoting anti-inflammatory immune responses. Yet, the underlying molecular mechanisms of commensal-mediated IL-10 production by regulatory B cells (Bregs) are not fully elucidated. Here, we demonstrate that bacterial CpG motifs trigger the signaling downstream of TLR9 promoting I\u03baBNS-mediated expression of Blimp-1, a transcription regulator of IL-10. Surprisingly, this effect was counteracted by the NF-\u03baB transcription factor c-Rel. A functional screen for intestinal bacterial species identified the commensal Clostridium sporogenes, secreting high amounts of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), as an amplifier of IL-10 production by promoting sustained mTOR signaling in B cells. Consequently, enhanced Breg functionality was achieved by combining CpG with the SCFA butyrate or the BCFA isovalerate thereby synergizing TLR- and mTOR-mediated pathways. Collectively, Bregs required two bacterial signals (butyrate and CpG) to elicit their full suppressive capacity and ameliorate T cell-mediated intestinal inflammation. Our study has dissected the molecular pathways induced by bacterial factors, which might contribute not only to better understanding of host-microbiome interactions, but also to exploration of new strategies for improvement of anti-inflammatory cellular therapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39265892\/?utm_source=Chrome&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20240929041234&amp;v=2.18.0.post9+e462414\">39265892<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2024.09.003\">10.1016\/j.mucimm.2024.09.003<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2024 Sep 16:S1933-0219(24)00096-5. doi: 10.1016\/j.mucimm.2024.09.003. Online ahead of print. ABSTRACT The host-microbiome axis has been implicated in promoting anti-inflammatory immune responses. Yet, the underlying molecular mechanisms of commensal-mediated IL-10 production by regulatory B cells (Bregs) are not fully elucidated. Here, we demonstrate that bacterial CpG motifs trigger the signaling downstream of TLR9 promoting &#8230; <a title=\"Dissecting the metabolic signaling pathways by which microbial molecules drive the differentiation of regulatory B cells. Maik Luu\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/dissecting-the-metabolic-signaling-pathways-by-which-microbial-molecules-drive-the-differentiation-of-regulatory-b-cells-maik-luu\/\" aria-label=\"Read more about Dissecting the metabolic signaling pathways by which microbial molecules drive the differentiation of regulatory B cells. Maik Luu\">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":[57,42],"tags":[],"class_list":["post-16917","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16917","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=16917"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16917\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16917"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16917"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16917"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}