{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:11:20Z","timestamp":1788966680961,"version":"build-2803163510"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"17","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Government | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:p>\n                    Chronic inflammatory skin disorders are characterized by keratinocyte hyperproliferation and hyperactivation as well as immune cell infiltration. We investigated whether immune cell\u2013derived acetylcholine (ACh) is a modulator of skin inflammation in mice. Here, we identify skin epithelial B cells as a key source of ACh that damps down inflammation. We used imiquimod (IMQ) to induce inflammatory skin disease (ISD) in mice lacking ACh production specifically in B cells (ChAT\n                    <jats:sup>fl\/fl;Mb1-Cre<\/jats:sup>\n                    mice). Increased keratinocyte proliferation, epidermal thickening, and elevated levels of proinflammatory cytokines resulted. ACh binding to \u03b19 nicotinic ACh receptor (encoded by\n                    <jats:italic>Chrna9<\/jats:italic>\n                    ) expressed on wild-type mouse keratinocytes reduced their proliferation.\n                    <jats:italic>Chrna9<\/jats:italic>\n                    -deficient mice exhibited the same exacerbated ISD phenotype as ChAT\n                    <jats:sup>fl\/fl;Mb1-Cre<\/jats:sup>\n                    mice following IMQ induction. Our data suggest that B cell\u2013derived ACh maintains skin homeostasis by modulating keratinocyte turnover and controlling immune-related inflammation. Therapeutic manipulation of this cholinergic pathway might mitigate both keratinocyte dysfunction and immune dysregulation in human patients, potentially pointing to treatments for ISDs such as psoriasis and related disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2501960122","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T13:37:33Z","timestamp":1745415453000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["B cell\u2013derived acetylcholine mitigates skin inflammation in mice through \u03b19 nicotinic acetylcholine receptor\u2013mediated signaling"],"prefix":"10.1073","volume":"122","author":[{"given":"Erica","family":"Foffi","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network","place":["Toronto, 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