{"id":21242,"date":"2025-01-03T07:12:01","date_gmt":"2025-01-03T06:12:01","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/01\/03\/targeting-the-ep2-receptor-ameliorates-inflammatory-bowel-disease-in-mice-by-enhancing-the-immunosuppressive-activity-of-treg-cells-chenchen-wang\/"},"modified":"2025-01-03T07:12:01","modified_gmt":"2025-01-03T06:12:01","slug":"targeting-the-ep2-receptor-ameliorates-inflammatory-bowel-disease-in-mice-by-enhancing-the-immunosuppressive-activity-of-treg-cells-chenchen-wang","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/01\/03\/targeting-the-ep2-receptor-ameliorates-inflammatory-bowel-disease-in-mice-by-enhancing-the-immunosuppressive-activity-of-treg-cells-chenchen-wang\/","title":{"rendered":"Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of Treg cells. Chenchen Wang"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2024 Dec 31:S1933-0219(24)00137-5. doi: 10.1016\/j.mucimm.2024.12.014. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T<sub>reg<\/sub>) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E<sub>2<\/sub> (PGE<sub>2<\/sub>), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner. However, whether PGE<sub>2<\/sub> regulates T<sub>reg<\/sub> cell function and contributes to IBD pathogenesis remains unclear. Here, we found that the PGE<sub>2<\/sub> receptor subtype 2 (EP2) is highly expressed in T<sub>reg<\/sub> cells. T<sub>reg<\/sub> cell-specific deletion of EP2 resulted in increased T<sub>reg<\/sub> cell numbers, and enhanced granzyme B(GzmB) expression and immunosuppressive capacity of T<sub>reg<\/sub> cells in mice. Adoptive transfer of EP2-deficient T<sub>reg<\/sub> cells attenuated na\u00efve CD4<sup>+<\/sup> T cell transfer-induced colitis in Rag1<sup>-\/-<\/sup> mice. Mice with EP2-deficient T<sub>reg<\/sub> cells were protected from 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sodium sulfate (DSS)-induced colitis. Pharmacological blockage of EP2 with PF-04418948 markedly alleviated DSS-induced colitis in mice in a T<sub>reg<\/sub>-dependent manner. Mechanistically, activation of EP2 suppressed T<sub>reg<\/sub> cell function, at least in part, through reduction of GzmB expression via PKA-mediated inhibition of NF-\u03baB signaling. Thus, we identified the PGE<sub>2<\/sub>\/EP2 axis as a key negative modulator of T<sub>reg<\/sub> cell function, suggesting EP2 inhibition as a potential therapeutic strategy for IBD treatment.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39746548\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20250103011159&amp;v=2.18.0.post9+e462414\">39746548<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2024.12.014\">10.1016\/j.mucimm.2024.12.014<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2024 Dec 31:S1933-0219(24)00137-5. doi: 10.1016\/j.mucimm.2024.12.014. Online ahead of print. ABSTRACT Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (Treg) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E2 (PGE2), a bioactive lipid compound derived from &#8230; <a title=\"Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of Treg cells. Chenchen Wang\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/01\/03\/targeting-the-ep2-receptor-ameliorates-inflammatory-bowel-disease-in-mice-by-enhancing-the-immunosuppressive-activity-of-treg-cells-chenchen-wang\/\" aria-label=\"Read more about Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of Treg cells. Chenchen Wang\">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-21242","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\/21242","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=21242"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/21242\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=21242"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=21242"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=21242"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}