{"id":19775,"date":"2024-11-26T06:59:23","date_gmt":"2024-11-26T05:59:23","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/11\/26\/gut-homing-and-intestinal-tigitnegcd38-memory-t-cells-acquire-an-il-12-induced-ex-th17-pathogenic-phenotype-in-a-subgroup-of-crohns-disease-patients-with-a-severe-disease-course-maud-heredia\/"},"modified":"2024-11-26T06:59:23","modified_gmt":"2024-11-26T05:59:23","slug":"gut-homing-and-intestinal-tigitnegcd38-memory-t-cells-acquire-an-il-12-induced-ex-th17-pathogenic-phenotype-in-a-subgroup-of-crohns-disease-patients-with-a-severe-disease-course-maud-heredia","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/11\/26\/gut-homing-and-intestinal-tigitnegcd38-memory-t-cells-acquire-an-il-12-induced-ex-th17-pathogenic-phenotype-in-a-subgroup-of-crohns-disease-patients-with-a-severe-disease-course-maud-heredia\/","title":{"rendered":"Gut-homing and intestinal TIGITnegCD38+ memory T cells acquire an IL-12-induced, ex-Th17 pathogenic phenotype in a subgroup of Crohn&#8217;s disease patients with a severe disease course. Maud Heredia"},"content":{"rendered":"<div>\n<p>Mucosal Immunol. 2024 Nov 23:S1933-0219(24)00116-8. doi: 10.1016\/j.mucimm.2024.11.008. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>CD4+ memory T cell (TM) reactivation drives chronicity in inflammatory bowel disease (IBD), including Crohn&#8217;s disease (CD) and ulcerative colitis. Defects driving loss of TM regulation likely differ between patients but remain undefined. In health, approximately 40 % of circulating gut-homing CD38+TM, express co-inhibitory receptor T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). TIGIT+CD38+TM have regulatory function while TIGITnegCD38+TM are enriched in IFN-\u03b3-producing cells. We hypothesized TIGITnegCD38+TM are inflammatory and drive disease in a subgroup of IBD patients. We characterized TIGIT+CD38+TM in a uniquely large cohort of pediatric IBD patients from time of diagnosis into adulthood. Circulating TIGITnegCD38+TM frequencies were higher in a subgroup of therapy-na\u00efve CD patients with high plasma IFN-\u03b3 and a more severe disease course. TIGITnegCD38+TM were highly enriched in HLA-DR+ and ex-Th17\/Th1-like cells, high producers of IFN-\u03b3. Cultures of healthy-adult-stimulated TM identified IL-12 as the only IBD-related inflammatory cytokine to drive the pathogenic ex-Th17-TIGITnegCD38+ phenotype. Moreover, IL12RB2 mRNA expression was higher in TIGITnegCD38+TM than TIGIT+CD38+TM, elevated in CD biopsies compared to controls, and correlated with severity of intestinal inflammation. Overall, we argue that in a subgroup of pediatric CD, increased IL-12 signaling drives reprogramming of Th17 to inflammatory Th1-like TIGITnegCD38+TM and causes more severe disease.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39586377\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20241126005922&amp;v=2.18.0.post9+e462414\">39586377<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2024.11.008\">10.1016\/j.mucimm.2024.11.008<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2024 Nov 23:S1933-0219(24)00116-8. doi: 10.1016\/j.mucimm.2024.11.008. Online ahead of print. ABSTRACT CD4+ memory T cell (TM) reactivation drives chronicity in inflammatory bowel disease (IBD), including Crohn&#8217;s disease (CD) and ulcerative colitis. Defects driving loss of TM regulation likely differ between patients but remain undefined. In health, approximately 40 % of circulating gut-homing CD38+TM, express &#8230; <a title=\"Gut-homing and intestinal TIGITnegCD38+ memory T cells acquire an IL-12-induced, ex-Th17 pathogenic phenotype in a subgroup of Crohn&#8217;s disease patients with a severe disease course. Maud Heredia\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/11\/26\/gut-homing-and-intestinal-tigitnegcd38-memory-t-cells-acquire-an-il-12-induced-ex-th17-pathogenic-phenotype-in-a-subgroup-of-crohns-disease-patients-with-a-severe-disease-course-maud-heredia\/\" aria-label=\"Read more about Gut-homing and intestinal TIGITnegCD38+ memory T cells acquire an IL-12-induced, ex-Th17 pathogenic phenotype in a subgroup of Crohn&#8217;s disease patients with a severe disease course. Maud Heredia\">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":[57,42],"tags":[],"class_list":["post-19775","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\/19775","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=19775"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19775\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=19775"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=19775"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=19775"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}