Diminished antigen-specific IgG1 and interleukin-6 production and acetylcholinesterase expression in combined M1 and M5 muscarinic acetylcholine receptor knockout mice

Immunological activation of T cells enhances synthesis of acetylcholine (ACh) and transcription of choline acetyltransferase (ChAT), M5 muscarinic ACh receptor (mAChR) and acetylcholinesterase (ACH). Stimulation of mAChRs on T and B cells causes oscillating Ca (2+) signaling and up-regulation of c-fos expression; moreover, M-1 mAChRs play a crucial role in the differentiation of CD8(+) T cells into cytolytic T lymphocytes. Collectively, these findings suggest that immune cell function is regulated by its own cholinergic system. Bearing that in mind, we tested whether immune function can be regulated via mAChR-mediated pathways by immunizing combined M, and M5 mAChR knockout (MI/ M5KO)and wild-type (WT) C57BL/6JJcl mice with ovalburnin (OVA) and measuring serum IgG(1) and IgM 1 wk later. We found that serum levels of total and anti-OVA-specific IgG, were significantly lower in M-1/M-5 KO than WT mice, though there was no difference in serum levels of total and anti-OVA-specific IgM between the two genotypes. Secretion of interleukin (IL)-6 from activated spleen cells was significantly reduced in M-1/M-5 KO mice, whereas there was no significant change in gamma interferon secretion. Expression of AChE mRNA was significantly reduced in activated spleen cells from M-1/M-5 KO mice. These results suggest that M-1 and/or M5 mAChRs are involved in regulating cytokine (e.g., IL-6) production, leading to modulation of antibody class switching from IgM to IgG(1), but are not involved in the initial generation of the antibody response. They also support the notion that a non-neuronal cholinergic system is involved in regulating immune cell function. (c) 2007 Elsevier B.V All rights reserved.