| First Author | Simard AR | Year | 2013 |
| Journal | Immunol Cell Biol | Volume | 91 |
| Issue | 3 | Pages | 195-200 |
| PubMed ID | 23399696 | Mgi Jnum | J:278273 |
| Mgi Id | MGI:6356452 | Doi | 10.1038/icb.2013.1 |
| Citation | Simard AR, et al. (2013) Differential modulation of EAE by alpha9*- and beta2*-nicotinic acetylcholine receptors. Immunol Cell Biol 91(3):195-200 |
| abstractText | 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 alpha7-nicotinic acetylcholine receptor (nAChR) subtype. We recently have shown that effector T cells and myeloid cells constitutively express mRNAs encoding nAChR alpha9 and beta2 subunits and found evidence for immune system roles for non-alpha7-nAChRs. In the present study, we assessed the effects of nAChR alpha9 or beta2 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 alpha9 subunit knock-out (KO) mice irrespective of nicotine treatment. On the other hand, beta2 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 beta2 KO mice, elevated proportions of CNS myeloid cells but decreased ratios of CNS macrophages/microglia in alpha9 or beta2 KO mice, and some changes in iNOS, TNF-alpha and IL-1beta mRNA levels in alpha9 KO and/or beta2 KO mice. Our data thus suggest that beta2*- and alpha9*-nAChRs, in addition to alpha7-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. |
