Zozulya Alla L, Ortler Sonja, Lee JangEun, Weidenfeller Christian, Sandor Matyas, Wiendl Heinz, Fabry Zsuzsanna
Department of Neurology, University of Würzburg, 97080 Würzburg, Germany.
J Neurosci. 2009 Jan 7;29(1):140-52. doi: 10.1523/JNEUROSCI.2199-08.2009.
Dendritic cells (DCs) appear in higher numbers within the CNS as a consequence of inflammation associated with autoimmune disorders, such as multiple sclerosis, but the contribution of these cells to the outcome of disease is not yet clear. Here, we show that stimulatory or tolerogenic functional states of intracerebral DCs regulate the systemic activation of neuroantigen-specific T cells, the recruitment of these cells into the CNS and the onset and progression of experimental autoimmune encephalomyelitis (EAE). Intracerebral microinjection of stimulatory DCs exacerbated the onset and clinical course of EAE, accompanied with an early T-cell infiltration and a decreased proportion of regulatory FoxP3-expressing cells in the brain. In contrast, the intracerebral microinjection of DCs modified by tumor necrosis factor alpha induced their tolerogenic functional state and delayed or prevented EAE onset. This triggered the generation of interleukin 10 (IL-10)-producing neuroantigen-specific lymphocytes in the periphery and restricted IL-17 production in the CNS. Our findings suggest that DCs are a rate-limiting factor for neuroinflammation.
由于与自身免疫性疾病（如多发性硬化症）相关的炎症，树突状细胞（DCs）在中枢神经系统（CNS）中的数量会增加，但这些细胞对疾病结局的影响尚不清楚。在此，我们表明脑内DCs的刺激或耐受性功能状态调节神经抗原特异性T细胞的全身激活、这些细胞向CNS的募集以及实验性自身免疫性脑脊髓炎（EAE）的发病和进展。脑内微量注射刺激性DCs会加剧EAE的发病和临床病程，伴有早期T细胞浸润以及脑内表达调节性FoxP3的细胞比例降低。相反，脑内微量注射经肿瘤坏死因子α修饰的DCs会诱导其耐受性功能状态，并延迟或预防EAE发病。这会触发外周产生白细胞介素10（IL-10）的神经抗原特异性淋巴细胞，并限制CNS中IL-17的产生。我们的研究结果表明，DCs是神经炎症的一个限速因素。
