M-acetylcholine Receptors Regulate Inflammatory Responses Through Arginases 1/2 in Zebrafish

Abstract Muscarinic acetylcholine receptors (mAChRs) are widely expressed in parasympathetic effector cells and have been proved to play vital roles in synaptic transmission, smooth muscle contraction, digestive secretion. However, there are relatively few literatures revealing the roles of mAChRs in inflammatory process, and its underlying regulatory mechanisms have not been elucidated. Taking the advantages of live imaging of zebrafish, we found that inhibition of mAChRs resulted in increased neutrophils recruitment and proinflammatory cytokines expression, whereas activation of mAChRs led to opposite outcome. Subsequently, we found that mAChRs regulated the expression of arginases (args), and pharmacological intervention of args level could reverse the effects of mAChRs on neutrophils migration and cytokines expression, suggesting that args are important downstream proteins of mAChRs that mediate its regulation of inflammatory response. In this study, we identified Args as novel downstream proteins of mAChRs in the inflammatory process, provided additional evidence for peripheral immune regulation of cholinergic receptors.