{"id":38780,"date":"2025-07-23T17:47:50","date_gmt":"2025-07-23T15:47:50","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/microbial-dysbiosis-sculpts-a-systemic-ilc3-il-17-axis-governing-lung-inflammatory-responses-ahmed-kabil\/"},"modified":"2025-07-23T17:47:50","modified_gmt":"2025-07-23T15:47:50","slug":"microbial-dysbiosis-sculpts-a-systemic-ilc3-il-17-axis-governing-lung-inflammatory-responses-ahmed-kabil","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/microbial-dysbiosis-sculpts-a-systemic-ilc3-il-17-axis-governing-lung-inflammatory-responses-ahmed-kabil\/","title":{"rendered":"Microbial dysbiosis sculpts a systemic ILC3\/IL-17 axis governing lung inflammatory responses. Ahmed Kabil"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2025 Jul 20:S1933-0219(25)00073-X. doi: 10.1016\/j.mucimm.2025.07.002. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Advancements in vaccination and sanitation have significantly reduced the prevalence and burden of infectious diseases; however, these benefits have coincided with a marked rise in autoimmune and allergic disorders. Recent studies have investigated these linked trends through the lens of host-microbiome alterations, proposing these shifts as a potential explanatory mechanism. Previously, we demonstrated that vancomycin-induced depletion of short-chain fatty acid (SCFA)-producing bacteria results in hyperactivation of ILC2s and exacerbated allergic responses. Here we investigate the effects of low-dose streptomycin on innate and adaptive immune cell populations and their activation states. Although streptomycin-treated mice exhibit normal allergic responses, they display heightened susceptibility to Th1\/Th17-mediated disease, specifically hypersensitivity pneumonitis (HP). This is characterized by a two-fold increase in ILC3s and Th17 cells in the lungs, alongside activation of antigen-presenting cells (APCs) at steady state-an effect that is further amplified upon exposure to HP-inducing agents. Shotgun metagenomic analysis revealed that streptomycin-induced dysbiosis reduces microbial diversity, depletes bile acid-metabolizing bacteria, and enriches for metabolic pathways involved in branched-chain amino acid biosynthesis, including leucine-a known activator of mTORC1. Strikingly, administration of the secondary bile acid metabolite isolithocholic acid (an inverse agonist of ROR\u03b3t), or an IL-23 neutralizing antibody, reverses the enhanced susceptibility to HP. Inhibition of mTORC1 significantly reduced Th17\/ILC3 responses and histopathology. Our findings underscore microbial equilibrium as a key determinant of susceptibility to HP and uncover a positive feedback loop between IL and 23-producing APCs and ILC3\/Th17 cells that mechanistically links dysbiosis to sustained type 3 inflammation, and we identify a simple, actionable means of intervention.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40695364\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20250723114748&amp;v=2.18.0.post9+e462414\">40695364<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2025.07.002\">10.1016\/j.mucimm.2025.07.002<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2025 Jul 20:S1933-0219(25)00073-X. doi: 10.1016\/j.mucimm.2025.07.002. Online ahead of print. ABSTRACT Advancements in vaccination and sanitation have significantly reduced the prevalence and burden of infectious diseases; however, these benefits have coincided with a marked rise in autoimmune and allergic disorders. Recent studies have investigated these linked trends through the lens of host-microbiome alterations, proposing &#8230; <a title=\"Microbial dysbiosis sculpts a systemic ILC3\/IL-17 axis governing lung inflammatory responses. Ahmed Kabil\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/microbial-dysbiosis-sculpts-a-systemic-ilc3-il-17-axis-governing-lung-inflammatory-responses-ahmed-kabil\/\" aria-label=\"Read more about Microbial dysbiosis sculpts a systemic ILC3\/IL-17 axis governing lung inflammatory responses. Ahmed Kabil\">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-38780","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\/38780","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=38780"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/38780\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=38780"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=38780"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=38780"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}