Differential Modulation Of Eae By Î±9*- And Î²2*- Nicotinic Acetylcholine Receptors
Nicotine is a potent inhibitor of the immune response and is protective against experimental autoimmune encephalomyelitis (EAE). Initial studies suggested that the cholinergic system modulates inflammation via the Î±7-nicotinic acetylcholine receptor (nAChR) subtype. We recently have shown that effector T cells and myeloid cells constitutively express mRNAs encoding nAChR Î±9 and Î²2 subunits and found evidence for immune system roles for non-Î±7-nAChRs. In the present study, we assessed the effects of nAChR Î±9 or Î²2 subunit gene deletion on EAE onset and severity, with or without nicotine treatment. We report again that disease onset is delayed and severity is attenuated in nicotine-treated, wild-type mice, an effect that also is observed in Î±9 subunit knock-out (KO) mice irrespective of nicotine treatment. On the other hand, Î²2 KO mice fail to recover from peak measures of disease severity regardless of nicotine treatment, despite retaining sensitivity to nicotine's attenuation of disease severity. Prior to disease onset, we found significantly less reactive oxygen species production in the central nervous system (CNS) of Î²2 KO mice, elevated proportions of CNS myeloid cells but decreased ratios of CNS macrophages/microglia in Î±9 or Î²2 KO mice, and some changes in iNOS, TNF-Î± and IL-1Î² mRNA levels in Î±9 KO and/or Î²2 KO mice. Our data thus suggest that Î²2*- and Î±9*-nAChRs, in addition to Î±7-nAChRs, have different roles in endogenous and nicotine-dependent modulation of immune functions and could be exploited as therapeutic targets to modulate inflammation and autoimmunity. Â© 2013 Australasian Society for Immunology Inc. All rights reserved.
Immunology and Cell Biology
Digital Object Identifier (DOI)
Simard, Alain R.; Gan, Yan; St-Pierre, Stephanie; Kousari, Ariana; Patel, Varun; Whiteaker, Paul; Morley, Barbara J.; Lukas, Ronald J.; and Shi, Fu Dong, "Differential Modulation Of Eae By Î±9*- And Î²2*- Nicotinic Acetylcholine Receptors" (2013). Neurobiology. 203.