B cell-derived acetylcholine mitigates skin inflammation in mice through α9 nicotinic acetylcholine receptor-mediated signaling.

ABSTRACT: Chronic inflammatory skin disorders are characterized by keratinocyte hyperproliferation and hyperactivation as well as immune cell infiltration. We investigated whether immune cell-derived 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^{fl/fl;Mb1-Cre} mice). Increased keratinocyte proliferation, epidermal thickening, and elevated levels of proinflammatory cytokines resulted. ACh binding to α9 nicotinic ACh receptor (encoded by Chrna9) expressed on wild-type mouse keratinocytes reduced their proliferation. Chrna9-deficient mice exhi

SUBMITTER: Foffi E 

PROVIDER: S-EPMC12054817 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature