{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:29:22Z","timestamp":1789522162710,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["FGWS-2024-0002"],"award-info":[{"award-number":["FGWS-2024-0002"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Serotonin (5-hydroxytryptamine, 5-HT) is traditionally considered a neurotransmitter, but most of the body\u2019s serotonin is peripheral and participates in vascular, hemostatic, inflammatory, and immune processes. This review summarizes current evidence on the role of peripheral serotonin in innate and adaptive immunity and evaluates its clinical relevance in inflammatory and immune-mediated diseases. The article synthesizes experimental and clinical data on serotonin sources, 5-HT receptors, SERT, serotonylation, and 5-HT-dependent regulation of neutrophils, monocytes\/macrophages, mast cells, dendritic cells, T cells, and B cells. The reviewed data indicate that serotonin modulates leukocyte recruitment, platelet\u2013immune interactions, NETosis, macrophage polarization, dendritic cell\u2013T-cell communication, lymphocyte activation, vascular permeability, and tissue remodeling. Clinically, serotonergic mechanisms are implicated in sepsis, inflammatory bowel disease, autoimmune disorders, cardiovascular inflammation, thromboinflammation, and the tumor microenvironment. However, the direction of 5-HT effects is not uniform and depends on receptor subtype, cell type, local mediator concentration, disease stage, and tissue context. Serotonin should therefore be regarded as a context-dependent immunoregulatory mediator rather than an exclusively pro- or anti-inflammatory factor. Further studies are needed to standardize clinical measurements of serotonin and its metabolites and to define therapeutically relevant serotonergic targets.<\/jats:p>","DOI":"10.3390\/cells15151353","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serotonin as a Regulator of Innate and Adaptive Immunity: Mechanisms and Clinical Relevance in Inflammatory Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4693-5624","authenticated-orcid":false,"given":"Vladimir","family":"Inozemtsev","sequence":"first","affiliation":[{"name":"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A. Negovsky Research Institute of General Reanimatology, 107031 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Shashkovskaya","sequence":"additional","affiliation":[{"name":"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A. Negovsky Research Institute of General Reanimatology, 107031 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-0845","authenticated-orcid":false,"given":"Viktoria","family":"Sergunova","sequence":"additional","affiliation":[{"name":"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A. Negovsky Research Institute of General Reanimatology, 107031 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.med.60.042307.110802","article-title":"The Expanded Biology of Serotonin","volume":"60","author":"Berger","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2017.51","article-title":"Non-Conventional Features of Peripheral Serotonin Signalling\u2014The Gut and Beyond","volume":"14","author":"Spohn","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Herr, N., Bode, C., and Duerschmied, D. (2017). The Effects of Serotonin in Immune Cells. Front. Cardiovasc. 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