{"id":79572,"date":"2026-10-17T01:18:10","date_gmt":"2026-10-16T23:18:10","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/10\/17\/ctla4-rs3087243-a-linked-haplotype-is-associated-with-increased-ctla-4-expression-and-suppressive-function-in-human-regulatory-t-cells\/"},"modified":"2026-10-17T01:18:10","modified_gmt":"2026-10-16T23:18:10","slug":"ctla4-rs3087243-a-linked-haplotype-is-associated-with-increased-ctla-4-expression-and-suppressive-function-in-human-regulatory-t-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/10\/17\/ctla4-rs3087243-a-linked-haplotype-is-associated-with-increased-ctla-4-expression-and-suppressive-function-in-human-regulatory-t-cells\/","title":{"rendered":"CTLA4 rs3087243-A-linked haplotype is associated with increased CTLA-4 expression and suppressive function in human regulatory T cells"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Oct 1;215(10):vkag276. doi: 10.1093\/jimmun\/vkag276.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>CTLA-4 is an inhibitory receptor on T cells that limits immune activation by competing with the co-stimulatory receptor CD28 for binding to CD80 and CD86 on antigen-presenting cells. Regulatory T cells (Tregs) employ CTLA-4-mediated transendocytosis as a key suppressive mechanism. Several CTLA4 polymorphisms are associated with autoimmune disease risk and may modulate CTLA-4 expression and function. Here, we analyzed samples from 155 genotyped subjects using flow cytometry and functional assays to determine how haplotypes formed by 3 CTLA4 single-nucleotide polymorphisms shape T-cell phenotype and function ex vivo. The autoimmune-protective CTLA4 rs5742909-rs231775-rs3087243 CAA haplotype was linked to increased intracellular CTLA-4 expression in both Tregs and conventional CD4+ T cells compared with CGG, CAG, and TAG haplotypes, implicating rs3087243 as the likely causal variant. The CAA haplotype was also associated with increased Treg frequencies. In Tregs from CAA\/CAA subjects, elevated steady-state CTLA-4 expression promoted enhanced early CTLA-4 surface mobilization following anti-CD3\/anti-CD28 stimulation. Moreover, na\u00efve Tregs from CAA\/CAA subjects more effectively suppressed na\u00efve CD4+ T-cell proliferation in the presence of CD80\/CD86-expressing dendritic cells. Collectively, these findings indicate that the rs3087243-A-linked CAA haplotype is associated with increased CTLA-4 expression and enhanced Treg function, providing a mechanistic explanation for its protective association with autoimmunity.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42886733\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20261016191810&amp;v=2.20.1\">42886733<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag276\">10.1093\/jimmun\/vkag276<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Oct 1;215(10):vkag276. doi: 10.1093\/jimmun\/vkag276. ABSTRACT CTLA-4 is an inhibitory receptor on T cells that limits immune activation by competing with the co-stimulatory receptor CD28 for binding to CD80 and CD86 on antigen-presenting cells. Regulatory T cells (Tregs) employ CTLA-4-mediated transendocytosis as a key suppressive mechanism. Several CTLA4 polymorphisms are associated with autoimmune &#8230; <a title=\"CTLA4 rs3087243-A-linked haplotype is associated with increased CTLA-4 expression and suppressive function in human regulatory T cells\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/10\/17\/ctla4-rs3087243-a-linked-haplotype-is-associated-with-increased-ctla-4-expression-and-suppressive-function-in-human-regulatory-t-cells\/\" aria-label=\"Read more about CTLA4 rs3087243-A-linked haplotype is associated with increased CTLA-4 expression and suppressive function in human regulatory T cells\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-79572","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\/79572","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=79572"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/79572\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=79572"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=79572"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=79572"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}