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.
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.
复制标题
在多发性硬化症的模型中，烟碱乙酰胆碱受体调节了CCR2+Ly6chigh促炎单核细胞和中性粒细胞对中枢神经系统的渗透。
DOI：
10.4049/jimmunol.1501613
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Simard AR
中科院分区：
文献类型：
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作者：
Jiang W;St-Pierre S;Roy P;Morley BJ;Hao J;Simard AR
髓系细胞，包括促炎性单核细胞和中性粒细胞，在多发性硬化（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的病理学中起重要作用。这些细胞在疾病发展的早期阶段浸润中枢神经系统（CNS），并促成与症状严重程度相关的炎症反应。因此，识别和理解可以调节促炎性髓样细胞的CNS浸润的新机制至关重要。烟碱型乙酰胆碱受体（nAChRs）因其免疫调节特性而受到越来越多的研究。在这项研究中，我们评估了尼古丁（一种nAChR配体）调节EAE小鼠骨髓、脾脏、血液和CNS内促炎性髓系细胞数量的能力。我们发现，尼古丁可显著抑制促炎单核细胞和中性粒细胞在已知这些细胞在疾病病理学中起关键作用的时间点浸润到CNS中。另一方面，尼古丁不影响其他单核细胞的扩增。我们还表明，尼古丁通过作用于α7和α9 nAChR亚型发挥这些作用。最后，尼古丁处理的EAE小鼠的脑中，分别参与促炎单核细胞和中性粒细胞趋化的趋化因子CCL 2和CXCL 2的mRNA转录水平在这些细胞大量浸润之前降低。总之，我们的数据提供的证据表明，nAChRs可以调节促炎细胞浸润到中枢神经系统，这可能是治疗神经炎性疾病的显着价值。
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.