{"id":24703,"date":"2025-02-18T01:14:16","date_gmt":"2025-02-18T00:14:16","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/02\/18\/topoisomerase-1-is-required-for-the-development-and-function-of-thymus\/"},"modified":"2025-02-18T01:14:16","modified_gmt":"2025-02-18T00:14:16","slug":"topoisomerase-1-is-required-for-the-development-and-function-of-thymus","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/02\/18\/topoisomerase-1-is-required-for-the-development-and-function-of-thymus\/","title":{"rendered":"Topoisomerase 1 is required for the development and function of thymus"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jan 1;214(1):23-39. doi: 10.1093\/jimmun\/vkae003. Epub 2025 Jan 23.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Thymus organogenesis is critical for proper maturation of developing T cells. In this study, we identified <i>Topoisomerase 1<\/i> (<i>Top1<\/i>) as a novel gene involved in thymus development and function. We created a mouse line with deletion of <i>Top1<\/i> in thymic epithelial cells (TECs) and our results demonstrate that biallelic loss of <i>Top1<\/i> in TECs causes congenital thymic aplasia, precipitating T cell immunodeficiency. Transcriptomic analysis provides insights into the molecular mechanism of <i>Top1<\/i> in thymus development as we identify key genes involved in thymus organogenesis as the transcriptional targets of <i>Top1<\/i> in TECs. Analysis of peripheral immunological compartments revealed severe loss of \u03b1\u03b2 T cells complemented with a disproportionate accumulation of \u03b3\u03b4 T cells and myeloid cells upon deletion of <i>Top1<\/i> in TECs. The residual \u03b1\u03b2 T cells in <i>Top1<\/i> knock-out mice were effector and oligoclonal in nature highlighting their self-reactivity. These results reveal a previously unknown role of <i>Top1<\/i> in thymus development and T cell homeostasis. We propose <i>Top1<\/i> as a genetic target for altered thymic development and T cell lymphopenia.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39959339\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250217191416&amp;v=2.18.0.post9+e462414\">39959339<\/a> | PMC:<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/PMC7617390\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250217191416&amp;v=2.18.0.post9+e462414\">PMC7617390<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkae003\">10.1093\/jimmun\/vkae003<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jan 1;214(1):23-39. doi: 10.1093\/jimmun\/vkae003. Epub 2025 Jan 23. ABSTRACT Thymus organogenesis is critical for proper maturation of developing T cells. In this study, we identified Topoisomerase 1 (Top1) as a novel gene involved in thymus development and function. We created a mouse line with deletion of Top1 in thymic epithelial cells (TECs) &#8230; <a title=\"Topoisomerase 1 is required for the development and function of thymus\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/02\/18\/topoisomerase-1-is-required-for-the-development-and-function-of-thymus\/\" aria-label=\"Read more about Topoisomerase 1 is required for the development and function of thymus\">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":[42,71],"tags":[],"class_list":["post-24703","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\/24703","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=24703"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/24703\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=24703"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=24703"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=24703"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}