Infiltration of CCR2+Ly6Chigh proinflammatory monocytes and neutrophils into the central nervous system is modulated by nicotinic acetylcholine receptors in a model of multiple sclerosis

Wei Jiang, Stephanie St-Pierre, Patrick Roy, Barbara J. Morley, Junwei Hao, Alain R. Simard

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Myeloid cells, including proinflammatory monocytes and neutrophils, have important roles in the pathology of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). These cells infiltrate the CNS in the early stages of disease development and contribute to the inflammatory response that is associated with symptom severity. It is thus crucial to identify and understand new mechanisms that can regulate the CNS infiltration of proinflammatory myeloid cells. Nicotinic acetylcholine receptors (nAChRs) have been increasingly studied for their immune-regulatory properties. In this study, we assessed the ability of nicotine, an nAChR ligand, to modulate proinflammatory myeloid cell numbers within the bone marrow, spleen, blood, and CNS of EAE mice. We found that nicotine significantly inhibits the infiltration of proinflammatory monocytes and neutrophils into the CNS at time points where these cells are known to play critical roles in disease pathology. In contrast, nicotine does not affect the expansion of other monocytes. We also show that nicotine exerts these effects by acting on α7 and α9 nAChR subtypes. Finally, mRNA transcript levels for CCL2 and CXCL2, chemokines involved in the chemotaxis of proinflammatory monocytes and neutrophils, respectively, are reduced in the brain of nicotine-treated EAE mice before the massive infiltration of these cells. Taken together, our data provide evidence that nAChRs can regulate proinflammatory cell infiltration into the CNS, which could be of significant value for the treatment of neuroinflammatory disorders.

Original languageEnglish (US)
Pages (from-to)2095-2108
Number of pages14
JournalJournal of Immunology
Volume196
Issue number5
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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