Roles of muscarinic acetylcholine receptors in interleukin-2 synthesis in lymphocytes

Receptors for many neurotransmitters including catecholamines and acetylcho line (ACh) have been detected on the cell surface of lymphocytes. It has be en demonstrated that a human T cell line synthesizes ACh and suggested that ACh may be an autacoid modulating T cell-dependent immune responses. Howev er, the biochemical interactions of the ACh system with the immune system h ave not been elucidated in detail. We have shown that mi and m2 muscarinic receptor mRNAs are expressed in human peripheral blood lymphocytes and in h uman T cell line Jurkat cells and that pretreatment of these cells with a m uscarinic receptor agonist enhances interleukin-2 (IL-2) production. We als o postulated possible intracellular signaling pathways via which muscarinic receptors regulate IL-2 production in Jurkat cells. The findings suggest t hat M-1 muscarinic receptors are involved in muscarinic receptor-mediated e nhancement of IL-2 production in Jurkat cells and that the transcription fa ctor AP-1 and pathways via mitogen-activated protein kinase (MAPK)/extracel lular signal regulated protein kinase and c-Jun N-terminal kinase, but not via p38 MAPK, may be involved in the muscarinic receptor-mediated enhanceme nt of IL-2 production. Our findings demonstrate a neuro-immune interaction through muscarinic receptor signaling in immune cells.