{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T11:15:38Z","timestamp":1793099738427,"version":"4.5.0"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P01DK119130 Core C"],"award-info":[{"award-number":["P01DK119130 Core C"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TRC4","award":["066"],"award-info":[{"award-number":["066"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>The anti-inflammatory cholinergic pathway describes the interaction between cholinergic vagal nerves and splenic immune cells, yet the exact mechanisms underlying the anti-inflammatory cholinergic pathway remain disputed. Here, we mapped the expression of key molecular components of the anti-inflammatory cholinergic pathway in the adult mouse using RNAScope in situ hybridization (ISH) and quantitative PCR (qPCR). In C57BL\/6J wild-type male mice, we observed the expression of choline acetyltransferase (<jats:italic><jats:italic>Chat<\/jats:italic><\/jats:italic>) and alpha 7 nicotinic acetylcholine receptor (<jats:italic><jats:italic>Chrna7<\/jats:italic><\/jats:italic>) in various autonomic neurons throughout the body, but not in the spleen, even after bacterial lipopolysaccharide (LPS) treatment. In contrast, the beta-2 adrenergic receptor (<jats:italic><jats:italic>Adrb2<\/jats:italic><\/jats:italic>), another autonomic receptor with well-documented anti-inflammatory actions, was highly expressed in the spleen, with a significant decrease following LPS administration. Interestingly, <jats:italic><jats:italic>Adrb2<\/jats:italic><\/jats:italic> was also expressed at lower levels in the spleen of a newly generated global knockout mouse for <jats:italic><jats:italic>Chrna7<\/jats:italic><\/jats:italic>. Lastly, we did not observe YFP-positive cells or axons in the spleen of the ChAT-Cre-ChR2-YFP mouse. Based on our findings, we propose a new model of the cholinergic anti-inflammatory pathway that highlights the roles of extrasplenic cholinergic signaling.<\/jats:p>","DOI":"10.1371\/journal.pone.0331707","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:22:38Z","timestamp":1757092958000},"page":"e0331707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic"],"prefix":"10.1371","volume":"20","author":[{"given":"Warda","family":"Merchant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Wyler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandy","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3609-7441","authenticated-orcid":true,"given":"Laurent","family":"Gautron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"issue":"3","key":"pone.0331707.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0214317","article-title":"Characterization of plasma cytokine response to intraperitoneally administered LPS & subdiaphragmatic branch vagus nerve stimulation in rat 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