SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205+ dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity

Takeshi Fujii, Kazuhide Horiguchi, Hiroshi Sunaga, Yasuhiro Moriwaki, Hidemi Misawa, Tadashi Kasahara, Shoutaro Tsuji, Koichiro Kawashima

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Immune cells often express various nicotinic ACh receptor (nAChR) subtypes, including α7 nAChRs, as well as mRNA encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide (SLURP)-1, an endogenous α7 nAChR allosteric ligand. We detected SLURP-1 immunoreactivity in CD205+ dendritic cells (DCs) residing in human tonsils. Phytohemagglutinin (PHA, 10μg/ml), a T cell activator, attenuated cell proliferation and increased the ACh content of MOLT-3 human leukemic T cells compared with the vehicle control. Methyllycaconitine (MLA, 100nM), a specific α7 nAChR antagonist, abolished all effects elicited by PHA. Recombinant (r)SLURP-1 (0.5μg/ml) attenuated peripheral blood mononuclear cell proliferation and increased ChAT gene expression and the ACh content in MOLT-3 cells compared with the control, all of which were abolished by MLA. This suggests SLURP-1 activates cholinergic transmission by potentiating ACh synthesis and its action at α7 nAChRs, thereby facilitating functional development of T cells. These findings support the notion that SLURP-1 acts as a key modulator of immune responses.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalJournal of Neuroimmunology
Volume267
Issue number1-2
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Acetylcholine
  • Methyllycaconitine
  • Mononuclear cells
  • Proliferation
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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