Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention
Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention
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DOI：
10.1016/j.ccell.2019.08.001
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发表时间：
2019-09-16
期刊：
影响因子：
50.3
通讯作者：
Heikenwalder, Mathias
中科院分区：
文献类型：
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作者：
O'Connor, Tracy;Zhou, Xiaolan;Heikenwalder, Mathias
在中枢神经系统淋巴瘤(CNSL)的发展过程中，淋巴瘤细胞(LCS)是如何侵袭大脑的，目前尚不清楚。我们发现，核因子-KB诱导的胶质细胞增殖症促进了免疫活性小鼠的CNSL。胶质细胞增多症增加了细胞黏附分子，从而增加了大脑中的LCS，但不足以诱导CNSL。星形胶质细胞来源的CCL19在胶质细胞增生症诱导的CNSL中是必需的。在小鼠中删除CCL19或从LCS中删除CCR7可阻止CNSL的发育。双光子显微镜显示LCS瞬时进入正常脑实质。星形胶质细胞CCL19促进LCS对实质CNS的滞留，从而促进CNSL的形成。与年轻的野生型小鼠相比，年老的胶质细胞增生性野生型小鼠更容易形成CNSL，在人类胶质细胞增生症和CNSL中都观察到星形细胞CCL19。因此，CCL19-CCR7的相互作用可能是CNSL年龄相关风险增加的基础。
How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-KB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.