{"id":36321,"date":"2025-06-27T00:48:45","date_gmt":"2025-06-26T22:48:45","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/therapeutic-potential-of-nrf2-activating-drug-rta-408-in-suppressing-t-cell-effector-responses-and-inflammatory-bowel-disease\/"},"modified":"2025-06-27T00:48:45","modified_gmt":"2025-06-26T22:48:45","slug":"therapeutic-potential-of-nrf2-activating-drug-rta-408-in-suppressing-t-cell-effector-responses-and-inflammatory-bowel-disease","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/therapeutic-potential-of-nrf2-activating-drug-rta-408-in-suppressing-t-cell-effector-responses-and-inflammatory-bowel-disease\/","title":{"rendered":"Therapeutic potential of NRF2 activating drug RTA-408 in suppressing T cell effector responses and inflammatory bowel disease"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jun 16:vkaf117. doi: 10.1093\/jimmun\/vkaf117. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>RTA-408, also known as Omaveloxolone, is an FDA-approved drug for treating Friedrich&#8217;s Ataxia, a neurological disorder. It is a triterpenoid compound that activates nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of cellular redox balance. In this study, we explored the impact of RTA-408 on T cells and evaluated its therapeutic potential in inflammatory bowel disease (IBD). In vitro activation of murine and human T cells in the presence of RTA-408 resulted in suppressed proliferation, reduced expression of IFN-\u03b3, cytotoxic granules and IL-17, but enhanced frequency of Foxp3+ Treg cells. Treatment of Nrf2-deficient T cells with RTA-408 revealed that while the reduction in CD69 expression, IL-2, and IFN-\u03b3 levels is NRF2-dependent, the suppression of T cell proliferation and granzyme B\/perforin expression occurs independently of NRF2. In vivo administration of RTA-408 alleviated the disease severity in DSS-induced colitis mice by decreasing colonic T cell counts and their inflammatory cytokine production. Additionally, ex vivo treatment of T cells from IBD patients with RTA-408 reduced their expansion and IL-17 expression. Transcriptomic and metabolic analyses revealed that RTA-408 reduces glycolysis and mitochondrial respiration in T cells and reprograms their metabolism towards pentose phosphate pathway and glutaminolysis. Our findings highlight the potential of RTA-408 as a modulator of T cell homeostasis, metabolism, and inflammation, supporting its repurposing for inflammatory diseases like IBD.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40570091\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250626184844&amp;v=2.18.0.post9+e462414\">40570091<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf117\">10.1093\/jimmun\/vkaf117<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jun 16:vkaf117. doi: 10.1093\/jimmun\/vkaf117. Online ahead of print. ABSTRACT RTA-408, also known as Omaveloxolone, is an FDA-approved drug for treating Friedrich&#8217;s Ataxia, a neurological disorder. It is a triterpenoid compound that activates nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of cellular redox balance. In this study, we explored the &#8230; <a title=\"Therapeutic potential of NRF2 activating drug RTA-408 in suppressing T cell effector responses and inflammatory bowel disease\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/27\/therapeutic-potential-of-nrf2-activating-drug-rta-408-in-suppressing-t-cell-effector-responses-and-inflammatory-bowel-disease\/\" aria-label=\"Read more about Therapeutic potential of NRF2 activating drug RTA-408 in suppressing T cell effector responses and inflammatory bowel disease\">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-36321","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\/36321","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=36321"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36321\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36321"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36321"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36321"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}