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

Yoshihito X. Fujii, Ayako Tashiro, Kumiko Arimoto, Hirofumi Fujigaya, Yasuhiro Moriwaki, Hidemi Misawa, Takeshi Fujii, Minoru Matsui, Tadashi Kasahara, Koichiro Kawashima

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Immunological activation of T cells enhances synthesis of acetylcholine (ACh) and transcription of choline acetyltransferase (ChAT), M5 muscarinic ACh receptor (mAChR) and acetylcholinesterase (AChE). Stimulation of mAChRs on T and B cells causes oscillating Ca2+-signaling and up-regulation of c-fos expression; moreover, M1 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 M1 and M5 mAChR knockout (M1/M5 KO) and wild-type (WT) C57BL/6JJcl mice with ovalbumin (OVA) and measuring serum IgG1 and IgM 1 wk later. We found that serum levels of total and anti-OVA-specific IgG1 were significantly lower in M1/M5 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 M1/M5 KO mice, whereas there was no significant change in gamma interferon secretion. Expression of AChE mRNA was significantly reduced in activated spleen cells from M1/M5 KO mice. These results suggest that M1 and/or M5 mAChRs are involved in regulating cytokine (e.g., IL-6) production, leading to modulation of antibody class switching from IgM to IgG1, 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.

Original languageEnglish
Pages (from-to)80-85
Number of pages6
JournalJournal of Neuroimmunology
Volume188
Issue number1-2
DOIs
Publication statusPublished - 2007 Aug 1

Keywords

  • Acetylcholine
  • Class switching
  • Cytokine
  • IgG
  • Muscarinic receptor
  • Non-neuronal cholinergic system

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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