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Cholinergic regulation of thymocyte negative selection

ABSTRACT: Acetylcholine (ACh) and its receptors (AChRs) are widely produced by various kinds of immune cells and fine-tune both innate and adaptive immune responses. However, whether cholinergic signaling regulates immune cell development is unclear. Here, we show that mouse CD4+CD8+ double-positive (DP) thymocytes express high levels of a9 nicotinic (n) AChR, and that this receptor controls the negative selection of thymocytes. Knock-out mice lacking a9 nAChR show an altered TCR repertoire and reduced CD4+ and CD8+ T cells in a mixed bone marrow chimera setting. Although thymic tuft cells, B cells, and a portion of T cells were all found to express choline acetyltransferase (ChAT) and so are sources of ACh in mouse thymus, T cell-derived ACh plays a more important regulatory role. Our results thus reveal a new mechanism of immune cell development control that involves lymphocyte-mediated cholinergic signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE260947 | GEO | 2025/03/17

REPOSITORIES: GEO

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