Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, PR China.
J Neuroimmunol. 2019 Aug 15;333:576967. doi: 10.1016/j.jneuroim.2019.576967. Epub 2019 May 16.
Chemokine ligand 26 (CCL26) is a member of the eotaxin family. It works by interacting exclusively with chemokine receptor 3 (CCR3) and acts as an eosinophil-selective chemoattractant. There is an emerging role for eotaxins in autoimmune diseases. Studies have reported that chemokine ligand 11 (CCL11) and CCL26 are upregulated in patients with neuromyelitis optica spectrum disorder (NMOSD) during remission, CCL26 levels appear to be decreased in relapsing-remitting multiple sclerosis (RRMS), whereas CCL26 levels are significantly increased in secondary progressive multiple sclerosis (SPMS), indicating that CCL26 participates in the pathogenesis of multiple sclerosis (MS). We investigated the levels of CCL26, CCR3 and claudin-5 (a marker of changes in BBB (blood-brain barrier) permeability) at different stages of experimental autoimmune encephalomyelitis (EAE) to explore the underlying immune mechanisms of EAE. Our results showed that the levels of CCL26 and CCR3 in EAE rats were significantly increased compared with those in the control group. The levels of CCL26 in the serum and in brain tissues as well as the protein expression of CCR3 in brain tissues were positively correlated with the inflammatory scores of brain tissues from EAE rats and were negatively correlated with the protein expression of claudin-5. We concluded that CCL26, which in turn binds to the receptor CCR3, showed pro-inflammatory effects and aggravated tissue damage involving BBB impairment, especially in the acute stage of EAE. Our study uncovers another possible immunopathological mechanism of MS and provides a possible target for immune therapy.
趋化因子配体 26（CCL26）是趋化因子家族的一员。它通过与趋化因子受体 3（CCR3）特异性相互作用，作为嗜酸性粒细胞选择性趋化因子起作用。趋化因子在自身免疫性疾病中具有新兴作用。研究报道，在缓解期的视神经脊髓炎谱系疾病（NMOSD）患者中，趋化因子配体 11（CCL11）和 CCL26 上调，在复发缓解型多发性硬化症（RRMS）中 CCL26 水平似乎降低，而在继发性进展型多发性硬化症（SPMS）中 CCL26 水平显著升高，表明 CCL26 参与多发性硬化症（MS）的发病机制。我们研究了实验性自身免疫性脑脊髓炎（EAE）不同阶段 CCL26、CCR3 和紧密连接蛋白 5（BBB（血脑屏障）通透性变化的标志物）的水平，以探讨 EAE 的潜在免疫机制。我们的结果表明，EAE 大鼠的 CCL26 和 CCR3 水平明显高于对照组。EAE 大鼠血清和脑组织中 CCL26 水平以及脑组织中 CCR3 蛋白表达与 EAE 大鼠脑组织炎症评分呈正相关，与紧密连接蛋白 5 蛋白表达呈负相关。我们得出结论，CCL26 与受体 CCR3 结合，表现出促炎作用，加重组织损伤，特别是在 EAE 的急性期，导致 BBB 受损。我们的研究揭示了 MS 的另一种可能的免疫病理机制，并为免疫治疗提供了一个可能的靶点。
