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 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, play different roles in endogenous and nicotine-dependent modulation of immune functions and could be exploited as therapeutic targets to modulate inflammation and autoimmunity.

Myeloid cells, including proinflammatory monocytes and neutrophils, have important roles in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). These cells infiltrate the central nervous system (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, a 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. On the other hand, 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 prior to 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.

It is increasingly clear that nicotinic acetylcholine receptors (nAChRs) are involved in immune regulation, and that their activation can protect against inflammatory diseases. Previous data have shown that nicotine diminishes the numbers of peripheral monocytes and macrophages, especially those of the pro-inflammatory phenotype. The goal of the present study was to determine if nicotine modulates the production of bone marrow -derived monocytes/macrophages. In this study, we first found that murine bone marrow cells express multiple nAChR subunits, and that the α7 and α9 nAChRs most predominant subtypes found in immune cells and their precursors. Using primary cultures of murine bone marrow cells, we then determined the effect of nicotine on monocyte colony-stimulating factor and interferon gamma (IFNγ)-induced monocyte production. We found that nicotine lowered the overall number of monocytes, and more specifically, inhibited the IFNγ-induced increase in pro-inflammatory monocytes by reducing cell proliferation and viability. These data suggested that nicotine diminishes the ratio of pro-inflammatory versus anti-inflammatory monocyte produced in the bone marrow. We thus confirmed this hypothesis by measuring cytokine expression, where we found that nicotine inhibited the production of the pro-inflammatory cytokines TNFα, IL-1β and IL-12, while stimulating the secretion of IL-10, an anti-inflammatory cytokine. Finally, nicotine also reduced the number of pro-inflammatory monocytes in the bone marrow of LPS-challenged mice. Overall, our data demonstrate that both α7 and α9 nAChRs are involved in the regulation of pro-inflammatory M1 monocyte numbers.

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future.

Le Centre franco-ontarien de folklore (Cfof) est un organisme provincial à but non lucratif qui se spécialise en folklore. Dans cet article, nous montrons comment cet organisme est à la croisée de plusieurs chemins. Il se situe entre le monde de la recherche, le devoir de la préservation et l’imposant besoin de diffusion du patrimoine oral franco-ontarien. Il compose avec le patrimoine immatériel, matériel et la culture populaire. Il est le résultat de l’intersection entre la connaissance savante et la connaissance populaire. L’étude de ce cas montre que les intersections disciplinaires ne sont pas uniquement un défi pour les universitaires et que, malgré certains obstacles, les spécialisations et les partenariats servent de renfort pour le domaine de l’ethnologie, tout comme pour les organismes communautaires qui cherchent à répondre à des besoins sociaux.