Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors

Alain R. Simard, Yan Gan, Stéphanie St-Pierre, Ariana Kousari, Varun Patel, Paul Whiteaker, Barbara J Morley, Ronald J. Lukas, Fu Dong Shi

Research output: Contribution to journalArticle

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Abstract

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 α7-nicotinic acetylcholine receptor (nAChR) subtype. We recently have shown that effector T cells and myeloid cells constitutively express mRNAs encoding nAChR α9 and β2 subunits and found evidence for immune system roles for non-α7-nAChRs. In the present study, we assessed the effects of nAChR α9 or β2 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 α9 subunit knock-out (KO) mice irrespective of nicotine treatment. On the other hand, β2 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 β2 KO mice, elevated proportions of CNS myeloid cells but decreased ratios of CNS macrophages/microglia in α9 or β2 KO mice, and some changes in iNOS, TNF-α and IL-1β mRNA levels in α9 KO and/or β2 KO mice. Our data thus suggest that β2*- and α9*-nAChRs, in addition to α7-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.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalImmunology and Cell Biology
Volume91
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Autoimmune Experimental Encephalomyelitis
Nicotinic Receptors
Nicotine
Knockout Mice
Central Nervous System
Myeloid Cells
Inflammation
Messenger RNA
Gene Deletion
Microglia
Autoimmunity
Interleukin-1
Cholinergic Agents
Immune System
Reactive Oxygen Species
Macrophages
T-Lymphocytes

Keywords

  • autoimmunity
  • cholinergic anti-inflammatory pathway
  • experimental autoimmune encephalomyelitis
  • inflammation
  • multiple sclerosis
  • nicotinic acetylcholine receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Simard, A. R., Gan, Y., St-Pierre, S., Kousari, A., Patel, V., Whiteaker, P., ... Shi, F. D. (2013). Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors. Immunology and Cell Biology, 91(3), 195-200. https://doi.org/10.1038/icb.2013.1

Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors. / Simard, Alain R.; Gan, Yan; St-Pierre, Stéphanie; Kousari, Ariana; Patel, Varun; Whiteaker, Paul; Morley, Barbara J; Lukas, Ronald J.; Shi, Fu Dong.

In: Immunology and Cell Biology, Vol. 91, No. 3, 01.03.2013, p. 195-200.

Research output: Contribution to journalArticle

Simard, AR, Gan, Y, St-Pierre, S, Kousari, A, Patel, V, Whiteaker, P, Morley, BJ, Lukas, RJ & Shi, FD 2013, 'Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors', Immunology and Cell Biology, vol. 91, no. 3, pp. 195-200. https://doi.org/10.1038/icb.2013.1
Simard AR, Gan Y, St-Pierre S, Kousari A, Patel V, Whiteaker P et al. Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors. Immunology and Cell Biology. 2013 Mar 1;91(3):195-200. https://doi.org/10.1038/icb.2013.1
Simard, Alain R. ; Gan, Yan ; St-Pierre, Stéphanie ; Kousari, Ariana ; Patel, Varun ; Whiteaker, Paul ; Morley, Barbara J ; Lukas, Ronald J. ; Shi, Fu Dong. / Differential modulation of EAE by α9*- and β2*- nicotinic acetylcholine receptors. In: Immunology and Cell Biology. 2013 ; Vol. 91, No. 3. pp. 195-200.
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