{"id":16996,"date":"2024-09-30T10:47:39","date_gmt":"2024-09-30T08:47:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/30\/csf1-dependent-macrophage-support-matrisome-and-epithelial-stress-induced-keratin-remodeling-in-eosinophilic-esophagitis-taylor-m-benson\/"},"modified":"2024-09-30T10:47:39","modified_gmt":"2024-09-30T08:47:39","slug":"csf1-dependent-macrophage-support-matrisome-and-epithelial-stress-induced-keratin-remodeling-in-eosinophilic-esophagitis-taylor-m-benson","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/30\/csf1-dependent-macrophage-support-matrisome-and-epithelial-stress-induced-keratin-remodeling-in-eosinophilic-esophagitis-taylor-m-benson\/","title":{"rendered":"CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis. Taylor M Benson"},"content":{"rendered":"<div>\n<p>Mucosal Immunol. 2024 Sep 27:S1933-0219(24)00099-0. doi: 10.1016\/j.mucimm.2024.09.006. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We found that macrophage accumulation precedes esophageal fibrosis in FS-EoE patients. We developed a FS-EoE model via chronic administration of oxazalone allergen, in a transgenic mouse over-expressing esophageal epithelial hIL-5 (L2-IL5OXA). These mice display striking histopathologic features congruent with that found in FS-EoE patients. Unbiased proteomic analysis, using a unique extracellular-matrix (ECM) focused technique, identified an inflammation-reactive provisional basal lamina membrane signature and this was validated in two independent EoE patient RNA-sequencing\/proteomic cohorts, supporting model significance. A wound healing signature was also observed involving hemostasis-associated molecules previously unnoted in EoE. We further identified the ECM glycoprotein, Tenascin-C (TNC), and the stress-responsive keratin-16 (KRT16) as IL-4 and IL-13 responsive mediators, acting as biomarkers of FS-EoE. To mechanistically address how the immune infiltrate shapes FS-EoE progression, we phenotyped the major immune cell subsets that coalesce with fibrosis in both the L2-IL5OXA mice and in FS-EoE patients. We found that macrophage are required for matrisome and cytoskeletal remodeling. Importantly, we show that macrophage accumulation precedes esophageal fibrosis and provide a novel therapeutic target in FS-EoE as their depletion with anti-CSF1 attenuated reactive matrisome and cytoskeletal changes. Thus, macrophage-based treatments and the exploration of TNC and KRT16 as biomarkers may provide novel therapeutic options for patients with fibrostenosis.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39343055\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20240930044738&amp;v=2.18.0.post9+e462414\">39343055<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2024.09.006\">10.1016\/j.mucimm.2024.09.006<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2024 Sep 27:S1933-0219(24)00099-0. doi: 10.1016\/j.mucimm.2024.09.006. Online ahead of print. ABSTRACT Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We &#8230; <a title=\"CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis. Taylor M Benson\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/30\/csf1-dependent-macrophage-support-matrisome-and-epithelial-stress-induced-keratin-remodeling-in-eosinophilic-esophagitis-taylor-m-benson\/\" aria-label=\"Read more about CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis. Taylor M Benson\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-16996","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\/16996","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"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=16996"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16996\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16996"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16996"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16996"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}