Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack.
Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack.
复制标题
DOI：
10.1093/braincomms/fcac044
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
Horng S
中科院分区：
文献类型：
--
作者：
Amatruda M;Chapouly C;Woo V;Safavi F;Zhang J;Dai D;Therattil A;Moon C;Villavicencio J;Gordon A;Parkos C;Horng S
星形细胞末足与血管周围空间内浸润性免疫细胞之间接触介导的相互作用尚未得到充分研究，但代表了针对中枢神经系统自身免疫性疾病和残疾的潜在监管检查点。反应性星形胶质细胞上调连接粘附分子-A，这是一种免疫球蛋白样细胞表面受体，通过其配体、整合素、淋巴细胞功能相关抗原 1 与 T 细胞结合。在这里，我们测试了星形细胞连接粘附分子-A在调节中枢神经系统自身炎症性疾病中的作用。在细胞共培养中，我们发现星形胶质细胞和 T 细胞之间的连接粘附分子 A 介导的信号传导增加了基质金属蛋白酶 2、C-C 基序趋化因子配体 2 和粒细胞巨噬细胞集落刺激因子、驱动淋巴细胞进入的促炎因子以及多发性硬化症和实验性自身免疫中的致病性的水平。 脑脊髓炎，中枢神经系统自身免疫性疾病的动物模型。在实验性自身免疫性脑脊髓炎中，与野生型对照相比，星形胶质细胞特异性 JAM-A 缺失 (mGFAP:CreJAM-Afl/fl) 的小鼠表现出基质金属蛋白酶-2 水平降低、T 细胞从血管周围间隙浸润中枢神经系统实质的能力降低以及较温和的组织病理学和临床病程 (JAM-Afl/fl)。通过腹腔注射可溶性连接粘附分子-A阻断肽治疗野生型小鼠，可降低实验性自身免疫性脑脊髓炎的严重程度，突显接触介导的星形胶质细胞-免疫细胞信号传导作为对抗神经炎症疾病的新型转化靶点的潜力。阿马特鲁达等人。报道称，星形细胞免疫细胞受体、连接粘附分子-A 会增加基质金属蛋白酶-2 的水平，并在自身免疫攻击期间促进 T 细胞进入中枢神经系统。阻断接触介导的星形胶质细胞免疫细胞信号代表了一种针对多发性硬化症和其他中枢神经系统自身炎症性疾病的新治疗方法。
Contact-mediated interactions between the astrocytic endfeet and infiltrating immune cells within the perivascular space are underexplored, yet represent potential regulatory check-points against CNS autoimmune disease and disability. Reactive astrocytes upregulate junctional adhesion molecule-A, an immunoglobulin-like cell surface receptor that binds to T cells via its ligand, the integrin, lymphocyte function-associated antigen-1. Here, we tested the role of astrocytic junctional adhesion molecule-A in regulating CNS autoinflammatory disease. In cell co-cultures, we found that junctional adhesion molecule-A-mediated signalling between astrocytes and T cells increases levels of matrix metalloproteinase-2, C–C motif chemokine ligand 2 and granulocyte-macrophage colony-stimulating factor, pro-inflammatory factors driving lymphocyte entry and pathogenicity in multiple sclerosis and experimental autoimmune encephalomyelitis, an animal model of CNS autoimmune disease. In experimental autoimmune encephalomyelitis, mice with astrocyte-specific JAM-A deletion (mGFAP:CreJAM-Afl/fl) exhibit decreased levels of matrix metalloproteinase-2, reduced ability of T cells to infiltrate the CNS parenchyma from the perivascular spaces and a milder histopathological and clinical course of disease compared with wild-type controls (JAM-Afl/fl). Treatment of wild-type mice with intraperitoneal injection of soluble junctional adhesion molecule-A blocking peptide decreases the severity of experimental autoimmune encephalomyelitis, highlighting the potential of contact-mediated astrocyte–immune cell signalling as a novel translational target against neuroinflammatory disease. Amatruda et al. report that the astrocytic immune cell receptor, junctional adhesion molecule-A, increases levels of matrix metalloproteinase-2 and promotes T-cell entry into the CNS during autoimmune attack. Blocking contact-mediated astrocyte immune cell signals represents a novel therapeutic approach against multiple sclerosis and other CNS autoinflammatory diseases.
登录
查看更多内容
影响因子：
12.7
作者：
Gharagozloo M;Smith MD;Jin J;Garton T;Taylor M;Chao A;Meyers K;Kornberg MD;Zack DJ;Ohayon J;Calabresi BA;Reich DS;Eberhart CG;Pardo CA;Kemper C;Whartenby KA;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
15.9
作者：
Horng, Sam;Therattil, Anthony;John, Gareth R.
通讯作者：
John, Gareth R.
影响因子：
8
作者：
Flemming, Sven;Luissint, Anny-Claude;Parkos, Charles A.
通讯作者：
Parkos, Charles A.
影响因子：
5.3
作者：
Bhowmick, Saurav;D'Mello, Veera;Abdul-Muneer, P. M.
通讯作者：
Abdul-Muneer, P. M.
GM-CSF通过改变中枢神经系统渗透细胞的组成来促进实验性自身免疫性脑脊髓炎的慢性残疾，但可用于疾病诱导。
DOI：
10.4049/jimmunol.1701484
发表时间：
2018-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Duncker PC;Stoolman JS;Huber AK;Segal BM
通讯作者：
Segal BM