CCR2Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system
CCR2Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system
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DOI：
10.1093/brain/awp144
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发表时间：
2009-09-01
期刊：
影响因子：
14.5
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
--
作者：
Mildner, Alexander;Mack, Matthias;Prinz, Marco
趋化因子受体CCR2对于中枢神经系统自身免疫的诱导起着至关重要的作用。然而，目前尚不清楚携带 CCR2 的细胞如何介导致病反应。通过将骨髓嵌合与基因靶向相结合，我们在实验性自身免疫性脑脊髓炎（中枢神经系统自身免疫模型）期间检测到 CCR2 对放射抗性细胞具有轻微的疾病调节作用，该作用独立于内皮细胞上的靶向 CCR2 表达。有趣的是，淋巴细胞上 CCR2 的缺失并不影响自身免疫性脱髓鞘。相比之下，实验性自身免疫性脑脊髓炎的诱导需要 CCR2 与辅助细胞的结合。 CCR2Ly-6C(hi) 单核细胞迅速募集到发炎的中枢神经系统，对于疾病的效应期至关重要。通过 CCR2 的参与选择性消除这种特定的单核细胞亚群，大大降低了中枢神经系统的自身免疫。总的来说，这些数据表明 CCR2Ly-6C(hi) 单核细胞在中枢神经系统自身免疫炎症过程中具有促进疾病的作用。
The chemokine receptor CCR2 plays a vital role for the induction of autoimmunity in the central nervous system. However, it remains unclear how the pathogenic response is mediated by CCR2-bearing cells. By combining bone marrow chimerism with gene targeting we detected a mild disease-modulating role of CCR2 during experimental autoimmune encephalomyelitis, a model for central nervous system autoimmunity, on radio-resistant cells that was independent from targeted CCR2 expression on endothelia. Interestingly, absence of CCR2 on lymphocytes did not influence autoimmune demyelination. In contrast, engagement of CCR2 on accessory cells was required for experimental autoimmune encephalomyelitis induction. CCR2Ly-6C(hi) monocytes were rapidly recruited to the inflamed central nervous system and were crucial for the effector phase of disease. Selective depletion of this specific monocyte subpopulation through engagement of CCR2 strongly reduced central nervous system autoimmunity. Collectively, these data indicate a disease-promoting role of CCR2Ly-6C(hi) monocytes during autoimmune inflammation of the central nervous system.