{"id":16919,"date":"2024-09-29T10:12:39","date_gmt":"2024-09-29T08:12:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/the-kynurenine-pathway-regulated-by-intestinal-innate-lymphoid-cells-mediates-postoperative-cognitive-dysfunction-wan-bing-dai\/"},"modified":"2024-09-29T10:12:39","modified_gmt":"2024-09-29T08:12:39","slug":"the-kynurenine-pathway-regulated-by-intestinal-innate-lymphoid-cells-mediates-postoperative-cognitive-dysfunction-wan-bing-dai","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/the-kynurenine-pathway-regulated-by-intestinal-innate-lymphoid-cells-mediates-postoperative-cognitive-dysfunction-wan-bing-dai\/","title":{"rendered":"The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction. Wan-Bing Dai"},"content":{"rendered":"<div>\n<p>Mucosal Immunol. 2024 Sep 7:S1933-0219(24)00095-3. doi: 10.1016\/j.mucimm.2024.09.002. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia\/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia\/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia\/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia\/surgery-induced cognitive impairment. Mechanistically, anesthesia\/surgery increases interferon-\u03b3 (IFN-\u03b3)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-\u03b3 or ILCs mitigate anesthesia\/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-\u03b3-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39251184\/?utm_source=Chrome&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20240929041234&amp;v=2.18.0.post9+e462414\">39251184<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2024.09.002\">10.1016\/j.mucimm.2024.09.002<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2024 Sep 7:S1933-0219(24)00095-3. doi: 10.1016\/j.mucimm.2024.09.002. Online ahead of print. ABSTRACT Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia\/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their &#8230; <a title=\"The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction. Wan-Bing Dai\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/the-kynurenine-pathway-regulated-by-intestinal-innate-lymphoid-cells-mediates-postoperative-cognitive-dysfunction-wan-bing-dai\/\" aria-label=\"Read more about The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction. Wan-Bing Dai\">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":[57,42],"tags":[],"class_list":["post-16919","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\/16919","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=16919"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16919\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16919"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16919"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16919"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}