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

• α7 nAChR allosteric ligand SLURP-1 was expressed in CD205+DCs in human tonsils.
• SLURP-1+CD205+DCs were localized in close proximity to CD4+ T cells.
• SLURP-1 attenuated cell growth and increased ACh synthesis in the MOLT-3 and MNLs.
• All the above effects elicited by SLURP-1 were abolished by α7 nAChR antagonist.
• These results suggest that SLURP-1 acts as a key modulator of immune responses.

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, 10 μg/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, 100 nM), a specific α7 nAChR antagonist, abolished all effects elicited by PHA. Recombinant (r)SLURP-1 (0.5 μg/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.