Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS) Daily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion, and migration of T lymphocytes were tested by flow cytometry in 57 MS patients and 19 healthy controls. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC), and on T cell polarization in PBMC/mdDC mixed cultures. We identified a significant correlation between mean PM10 levels and expression of CCR6 CD4+ T circulating cells in MS patients. This was paralleled by the observation in vitro of a higher level of CCR6 expression on PBMC following treatment with increased doses of particulate matter. Moreover, in mdDC cultures, particulate matter induced the secretion by mdDC of Th17 polarizing IL1 beta, IL6, and IL23 and, in mdDC/PBMC mixed cultures, enhanced generation of IL17-producing T cells. Ex vivo and in vitro studies support the pro-inflammatory role of PM in MS, by upregulating expression of CCR6 on circulating CD4+ T cells and inducing in innate immune cells the production of Th17 polarizing cytokines. Therefore, we speculate that in MS respiratory exposure to PM10 may induce the production in the lung of autoreactive Th17 lymphocytes and boost their migratory properties through the blood-brain barrier.

中文翻译：

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空气污染导致多发性硬化症的炎症活动

最近，空气污染被确定为多发性硬化症的危险因素。本研究的目的是研究空气污染（即暴露于颗粒物 10 (PM10) 与多发性硬化症 (MS) 的炎症活动）之间临床关联的潜在免疫机制。科目。通过流式细胞术在 57 名 MS 患者和 19 名健康对照中测试了参与 T 淋巴细胞活化、粘附和迁移的分子的表达。我们接下来在体外评估了 PM10 对外周血单核细胞 (PBMC) CC 趋化因子受体 6 (CCR6) 表达、单核细胞衍生树突细胞 (mdDC) 细胞因子产生的影响，以及对 PBMC/mdDC 中 T 细胞极化的影响混合文化。我们发现 MS 患者的平均 PM10 水平与 CCR6 CD4+ T 循环细胞的表达之间存在显着相关性。这与在体外观察到在用增加剂量的颗粒物处理后 PBMC 上更高水平的 CCR6 表达相平行。此外，在 mdDC 培养物中，颗粒物质诱导了 Th17 极化 IL1 β、IL6 和 IL23 的 mdDC 分泌，并且在 mdDC/PBMC 混合培养物中，增强了产生 IL17 的 T 细胞的生成。体外和体外研究支持 PM 在 MS 中的促炎作用，通过上调循环 CD4+ T 细胞上 CCR6 的表达并诱导先天免疫细胞产生 Th17 极化细胞因子。所以，