{"id":40442,"date":"2025-08-13T06:47:59","date_gmt":"2025-08-13T04:47:59","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/direct-in-nod-genetic-ablation-of-bcl3-leads-to-complete-type-1-diabetes-protection\/"},"modified":"2025-08-13T06:47:59","modified_gmt":"2025-08-13T04:47:59","slug":"direct-in-nod-genetic-ablation-of-bcl3-leads-to-complete-type-1-diabetes-protection","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/direct-in-nod-genetic-ablation-of-bcl3-leads-to-complete-type-1-diabetes-protection\/","title":{"rendered":"Direct-in-NOD genetic ablation of Bcl3 leads to complete type 1 diabetes protection"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Aug 12:vkaf189. doi: 10.1093\/jimmun\/vkaf189. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>It was previously reported that genetic ablation of the NF-\u03baB atypical inhibitor Bcl3 through congenic introduction of a 129P2-embryo derived knockout allele (Bcl3tm1Ver) accelerated autoimmune diabetes in the NOD mouse model. Conversely, we found that direct CRISPR-mediated ablation of this gene in the NOD\/ShiLtDvs substrain completely inhibited diabetes development. Our CRISPR approach excised exons 3-7 within the NOD Bcl3 gene. These new NOD-Bcl3-\/- mice had very low levels of insulitis, indicating protective mechanisms elicited early in the disease process. Dissimilar to reports of Bcl3 ablation in nonautoimmune C57BL\/6-background mice, we found that splenic and lymph node B cells were not reduced. However, splenic T2 and MZ cells were increased with a disruption of B-cell follicle formation. Diabetes protection was associated with elevated splenic and lymph node regulatory T cells, and increases in CD4 effector and CD8 central memory T cells in pancreatic lymph nodes. Diabetes protection was overridden by anti-PD-1 administration. Previous studies suggested that Bcl3 may influence diabetes development downstream of Nfkbid, another atypical NF-\u03baB inhibitor. Indeed, co-introduction of this Bcl3 knockout allele also completely blocked diabetes in NOD-Nfkbid-\/- mice normally characterized by accelerated disease. Collectively these findings support the possibility that prior findings may have been driven by congenic introduction of linked modifier genes from non-NOD background strains and initiate a critical reevaluation of the role of Bcl3 in type 1 diabetes pathogenesis.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40796308\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250813004755&amp;v=2.18.0.post9+e462414\">40796308<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf189\">10.1093\/jimmun\/vkaf189<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Aug 12:vkaf189. doi: 10.1093\/jimmun\/vkaf189. Online ahead of print. ABSTRACT It was previously reported that genetic ablation of the NF-\u03baB atypical inhibitor Bcl3 through congenic introduction of a 129P2-embryo derived knockout allele (Bcl3tm1Ver) accelerated autoimmune diabetes in the NOD mouse model. Conversely, we found that direct CRISPR-mediated ablation of this gene in the &#8230; <a title=\"Direct-in-NOD genetic ablation of Bcl3 leads to complete type 1 diabetes protection\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/08\/13\/direct-in-nod-genetic-ablation-of-bcl3-leads-to-complete-type-1-diabetes-protection\/\" aria-label=\"Read more about Direct-in-NOD genetic ablation of Bcl3 leads to complete type 1 diabetes protection\">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":[42,71],"tags":[],"class_list":["post-40442","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\/40442","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=40442"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/40442\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=40442"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=40442"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=40442"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}