Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans Cells

Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans Cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans Cells Yungling Lee, Yeh Fong Tan, Chen-Yun Yeh, Sheng-Yun Hsu, Chun-Hao Lu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5628384/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Anecdotal evidence has suggested an association between psychiatric drugs and psoriasis but consensus is absent due to contradicting reports and the mechanism remains poorly defined. Here, we investigated the role played by serotonin 2A receptor (HTR2A), a receptor commonly targeted by psychiatric drugs, in regulating psoriasis. HTR2A antagonistic drugs worsened psoriatic outcome and HTR2A modulation reduced psoriatic inflammation. Using Imiquimod-induced psoriasiform model, HTR2A-deficient mice experienced exacerbated inflammation. Hematopoietic cells, particularly monocyte-derived Langerhans cells (moLC), were responsible for this phenotype. Mechanistically, the exacerbated inflammation is due to increased interleukin-23 (IL-23) secretion and HTR2A suppresses it by inhibiting activation of the non-canonical NFkB pathway. Serotonin is the putative agonist modulating HTR2A attenuating psoriatic inflammation. Lastly, our findings in mice were also validated clinically. Our data demonstrate serotonin modulates HTR2A, attenuating psoriatic inflammation by suppressing IL-23 secretion via inhibiting non-canonical NFkB pathway in moLCs. Biological sciences/Immunology/Autoimmunity Biological sciences/Immunology/Innate immune cells/Dendritic cells/Langerhans cells Full Text Additional Declarations Yes there is potential Competing Interest. Tsen-Fang Tsai has conducted clinical trials or received honoraria for serving as a consultant for AbbVie, AnaptysBio, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GlaxoSmithKline-Stiefel, Janssen-Cilag, Leo-Pharma, Merck, Novartis, PharmaEssentia, Pfizer, Sanofi, Sun Pharma and UCB. The remaining authors state no conflict of interest. Supplementary Files GEODataset.pdf GEO Dataset Information 20241209Supplementalinformation.pdf Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans Cells Supplemental Information NCOMMS2482399rs.pdf Reporting Summary Cite Share Download PDF Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5628384","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":396933377,"identity":"71776a58-f29f-4b11-8447-94509888f320","order_by":0,"name":"Yungling 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