{"id":33312,"date":"2025-05-23T12:51:39","date_gmt":"2025-05-23T10:51:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/23\/modulatory-effects-of-m3-muscarinic-acetylcholine-receptor-on-inflammatory-profiles-of-human-memory-t-helper-cells\/"},"modified":"2025-05-23T12:51:39","modified_gmt":"2025-05-23T10:51:39","slug":"modulatory-effects-of-m3-muscarinic-acetylcholine-receptor-on-inflammatory-profiles-of-human-memory-t-helper-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/23\/modulatory-effects-of-m3-muscarinic-acetylcholine-receptor-on-inflammatory-profiles-of-human-memory-t-helper-cells\/","title":{"rendered":"Modulatory effects of M3 muscarinic acetylcholine receptor on inflammatory profiles of human memory T helper cells"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 May 22:vkaf086. doi: 10.1093\/jimmun\/vkaf086. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Memory T helper (Th) cells, generated in response to immunogenic challenges, are crucial in orchestrating adaptive immune responses. Acetylcholine (ACh), a key neurotransmitter of the parasympathetic nervous system, modulates immune function via muscarinic ACh receptors (mAChRs). This study investigates the role of mAChRs, particularly the M3 muscarinic ACh receptor (M3R), in regulating the cytokine and chemokine profile and NF-\u03baB p65 activity in primary human memory Th cells. Memory Th cells were isolated from healthy donors and stimulated with anti-CD3\/CD28\/CD2 in the presence of oxotremorine-M (M1R-M5R agonist), atropine (M1R-M5R antagonist), or J104129 (M3R-selective antagonist). CHRM1-CHRM5 expression was quantified using RT-qPCR. M3R and phosphorylated NF-\u03baB p65 were analyzed by Western blot. IFN-\u03b3, IL-17A, and IL-4 were assessed by ELISA, while intracellular cytokine and chemokine receptor expression were measured by flow cytometry. CHRM3 knockout was performed using CRISPR-Cas9. Memory Th cells expressed all 5 mAChR subtypes. Oxotremorine-M increased IFN-\u03b3 and IL-17A while reducing IL-4 in an atropine-sensitive manner. Blocking or knocking out M3R prevented oxotremorine-M-induced increases in IFN-\u03b3 and IL-17A, but the suppression of IL-4 remained unchanged. Stimulation of mAChRs, particularly M3R, enhanced NF-\u03baB p65 activity but did not affect chemokine receptor expression, cell proliferation, viability, or M3R levels. These findings indicate that mAChRs, including M3R, drive a pro-inflammatory memory Th-cell response through NF-\u03baB p65 activation, while IL-4 suppression occurs independently of M3R. Targeting M3R specifically may provide a strategy for modulating adaptive immunity and treating inflammatory diseases.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40405417\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250523065131&amp;v=2.18.0.post9+e462414\">40405417<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf086\">10.1093\/jimmun\/vkaf086<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 May 22:vkaf086. doi: 10.1093\/jimmun\/vkaf086. Online ahead of print. ABSTRACT Memory T helper (Th) cells, generated in response to immunogenic challenges, are crucial in orchestrating adaptive immune responses. Acetylcholine (ACh), a key neurotransmitter of the parasympathetic nervous system, modulates immune function via muscarinic ACh receptors (mAChRs). This study investigates the role of mAChRs, &#8230; <a title=\"Modulatory effects of M3 muscarinic acetylcholine receptor on inflammatory profiles of human memory T helper cells\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/23\/modulatory-effects-of-m3-muscarinic-acetylcholine-receptor-on-inflammatory-profiles-of-human-memory-t-helper-cells\/\" aria-label=\"Read more about Modulatory effects of M3 muscarinic acetylcholine receptor on inflammatory profiles of human memory T helper cells\">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":[42,71],"tags":[],"class_list":["post-33312","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\/33312","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=33312"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33312\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=33312"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=33312"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=33312"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}