Cédile Oriane, Wlodarczyk Agnieszka, Owens Trevor
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
APMIS. 2017 Nov;125(11):945-956. doi: 10.1111/apm.12740. Epub 2017 Aug 24.
CCL2 is a chemokine that can be induced during neuroinflammation to recruit immune cells, but its role in the central nervous system (CNS) is unclear. Our aim was to better understand its role. We induced CCL2 in CNS of naive CCL2-deficient mice using intrathecally administered replication-defective adenovirus and examined cell infiltration by flow cytometry. CCL2 expression induced pronounced and unexpected recruitment of regulatory and IFNγ-producing T cells to CNS from blood, possibly related to defective egress of monocytes from CCL2-deficient bone marrow. Infiltration also occurred in mice lacking CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine-recruited T cells did not lead to CNS pathology. Our findings show a role for CCL2 in recruitment of CD4 T cells to the CNS and show that redundancy among chemokine receptors ensures optimal response.
CCL2是一种趋化因子，可在神经炎症期间被诱导以募集免疫细胞，但其在中枢神经系统（CNS）中的作用尚不清楚。我们的目的是更好地了解其作用。我们通过鞘内注射复制缺陷型腺病毒在未感染的CCL2缺陷小鼠的中枢神经系统中诱导CCL2表达，并通过流式细胞术检测细胞浸润情况。CCL2表达诱导了调节性T细胞和产生IFNγ的T细胞从血液中大量且意外地募集到中枢神经系统，这可能与CCL2缺陷骨髓中单核细胞的流出缺陷有关。在缺乏CCL2受体CCR2的小鼠中也发生了浸润。CCL2的另一种受体CCR4以及同样被诱导的CXCL10受体CXCR3在CCL2处理的中枢神经系统中的表达均增加。CCR4由神经元、星形胶质细胞以及CD4 T细胞表达，CXCR3由CD4和CD8 T细胞表达。趋化因子募集的T细胞并未导致中枢神经系统病理变化。我们的研究结果表明CCL2在将CD4 T细胞募集到中枢神经系统中发挥作用，并表明趋化因子受体之间的冗余确保了最佳反应。
