Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors.

A considerable number of in vivo studies have demonstrated that the cholinergic system can dampen the peripheral immune response, and it is thought that the α7-nicotinic acetylcholine receptor (nAChR) subtype is a key mediator of this process. The goal of the present study was to determine if nicotine modulates immunological mechanisms known to be involved in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for CNS autoimmune disease, via α7-nAChRs. Here we show that nicotine exposure attenuates EAE severity and that this effect is largely abolished in nAChR α7 subunit knock-out mice. However, nicotine exposure partially retains the ability to reduce lymphocyte infiltration into the CNS, inhibit auto-reactive T cell proliferation and helper T cell cytokine production, down-regulate co-stimulatory protein expression on myeloid cells, and increase the differentiation and recruitment of regulatory T cells, even in the absence of α7-nAChRs. Diverse effects of nicotine on effector and regulatory T cells, as well as antigen-presenting cells, may be linked to differential expression patterns of nAChR subunits across these cell types. Taken together, our data show that although α7-nAChRs indeed seem to play an important role in nicotine-conferred reduction of the CNS inflammatory response and protection against EAE, other nAChR subtypes also are involved in the anti-inflammatory properties of the cholinergic system.