{"id":44354,"date":"2025-09-30T12:00:00","date_gmt":"2025-09-30T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/identification-of-potential-therapeutic-agents-for-type-i-interferonopathy-using-ipsc-based-disease-modeling\/"},"modified":"2025-09-30T12:00:00","modified_gmt":"2025-09-30T10:00:00","slug":"identification-of-potential-therapeutic-agents-for-type-i-interferonopathy-using-ipsc-based-disease-modeling","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/identification-of-potential-therapeutic-agents-for-type-i-interferonopathy-using-ipsc-based-disease-modeling\/","title":{"rendered":"Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling"},"content":{"rendered":"<div>\n<p><b>J Clin Immunol<\/b>. 2025 Sep 30;45(1):140. doi: 10.1007\/s10875-025-01933-8.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs).<\/p>\n<p>METHODS: The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-\u03b1 secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs.<\/p>\n<p>RESULTS: Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-\u03b1 secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-\u03b1 secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-\u03b1 secretion from IFIH1 R779H-mutated DCs.<\/p>\n<p>CONCLUSION: Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41026253\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20250930143843&amp;v=2.18.0.post9+e462414\">41026253<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-025-01933-8\">10.1007\/s10875-025-01933-8<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2025 Sep 30;45(1):140. doi: 10.1007\/s10875-025-01933-8. ABSTRACT PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a &#8230; <a title=\"Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/identification-of-potential-therapeutic-agents-for-type-i-interferonopathy-using-ipsc-based-disease-modeling\/\" aria-label=\"Read more about Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling\">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":[69,42],"tags":[],"class_list":["post-44354","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44354","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=44354"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44354\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=44354"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=44354"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=44354"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}