{"id":58271,"date":"2026-03-11T06:37:04","date_gmt":"2026-03-11T05:37:04","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/11\/optimized-hookworm-derived-biologic-aip-2ntq48-restores-mucosal-tolerance-and-down-regulates-colon-cancer-associated-gene-expression-in-tnbs-induced-colitis-yan-lu\/"},"modified":"2026-03-11T06:37:04","modified_gmt":"2026-03-11T05:37:04","slug":"optimized-hookworm-derived-biologic-aip-2ntq48-restores-mucosal-tolerance-and-down-regulates-colon-cancer-associated-gene-expression-in-tnbs-induced-colitis-yan-lu","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/11\/optimized-hookworm-derived-biologic-aip-2ntq48-restores-mucosal-tolerance-and-down-regulates-colon-cancer-associated-gene-expression-in-tnbs-induced-colitis-yan-lu\/","title":{"rendered":"Optimized hookworm-derived biologic, AIP-2NTQ48 restores mucosal tolerance and down-regulates colon cancer-associated gene expression in TNBS-induced colitis. Yan Lu"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2026 Mar 8:S1933-0219(26)00029-2. doi: 10.1016\/j.mucimm.2026.03.005. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The development of treatments for ulcerative colitis (UC) has seen significant advancements over recent years, focusing on new drugs, innovative approaches, and a deeper understanding of the disease mechanisms. Few however have been able to restore natural tolerance. The hookworm-derived recombinant Anti-Inflammatory Protein (AIP)-2 has been previously shown to have promising pro-tolerogenic characteristics against asthma. Here we show that AIP-2 suppresses weight loss, colon damage, mucosal erosion and necrosis as well as the suppression of pro-inflammatory cytokines IL-6 and IFN-\u03b3 in a TNBS-induced model of UC. Following sequence optimization and efficacy comparison, we have generated the construct AIP-2<sub>NTQ48<\/sub> which contains the N-terminal sequence and an amino acid substitution (asparagine to glutamine) at position 48 to remove the N-glycan. AIP-2<sub>NTQ48<\/sub> significantly suppressed colon Th1\/Th17 pathways and promoted regulatory T cells via TGF-\u03b2, IL-10 and ICOSL signaling in colon tissues. Transcriptomics analysis revealed differential expression of genes from the TNF receptor superfamily, TNF-\u03b1-induced genes and aldehyde dehydrogenase (ALDH) encoding enzymes which promoted tissue repair and the suppression of colorectal cancer-causing pathways. This suggests that AIP-2<sub>NTQ48<\/sub> promotes Treg\/Th17 balance that could potentially offer a novel disease modifying therapeutic opportunity against UC.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41806940\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20260311013653&amp;v=2.19.0.post6+133c1fe\">41806940<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2026.03.005\">10.1016\/j.mucimm.2026.03.005<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2026 Mar 8:S1933-0219(26)00029-2. doi: 10.1016\/j.mucimm.2026.03.005. Online ahead of print. ABSTRACT The development of treatments for ulcerative colitis (UC) has seen significant advancements over recent years, focusing on new drugs, innovative approaches, and a deeper understanding of the disease mechanisms. Few however have been able to restore natural tolerance. The hookworm-derived recombinant Anti-Inflammatory Protein &#8230; <a title=\"Optimized hookworm-derived biologic, AIP-2NTQ48 restores mucosal tolerance and down-regulates colon cancer-associated gene expression in TNBS-induced colitis. Yan Lu\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/11\/optimized-hookworm-derived-biologic-aip-2ntq48-restores-mucosal-tolerance-and-down-regulates-colon-cancer-associated-gene-expression-in-tnbs-induced-colitis-yan-lu\/\" aria-label=\"Read more about Optimized hookworm-derived biologic, AIP-2NTQ48 restores mucosal tolerance and down-regulates colon cancer-associated gene expression in TNBS-induced colitis. Yan Lu\">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-58271","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\/58271","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=58271"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/58271\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=58271"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=58271"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=58271"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}