CCL20/CCR6 chemokine signaling is not essential for pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis
CCL20/CCR6 chemokine signaling is not essential for pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis
复制标题
CCL20/CCR6趋化因子信号传导对于多发性硬化症实验性自身免疫性脑脊髓炎小鼠模型的发病机制不是必需的
DOI：
10.1016/j.bbrc.2022.11.088
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发表时间：
2023
影响因子：
3.1
通讯作者：
Kobayashi Takashi
中科院分区：
文献类型：
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作者：
Sachi Nozomi;Kamiyama Naganori;Saechue Benjawan;Ozaka Sotaro;Dewayani Astri;Ariki Shimpei;Chalalai Thanyakorn;Soga Yasuhiro;Fukuda Chiaki;Kagoshima Yomei;Ekronarongchai Supanuch;Kobayashi Takashi
多发性硬化症是一种自身免疫性疾病，其中免疫系统攻击神经髓鞘。致病性Th 17细胞和调节性Treg细胞之间的平衡对于确定疾病活性至关重要，两者都表达趋化因子受体CCR 6。据推测，血脑屏障产生的CCR 6的同源配体CCL 20将这些免疫细胞吸引到中枢神经系统（CNS）。然而，CCR 6敲除（KO）小鼠中多发性硬化实验模型的病理表型尚不确定，而这在CCL 20-KO小鼠中尚未得到解决。为了解决这一问题，我们使用CRISPR/Cas9系统产生了CCL 20-KO和CCR 6-KO小鼠。实验性自身免疫性脑脊髓炎（EAE）在慢性期的临床表型在两个突变小鼠相对于野生型（WT）小鼠轻微加重。KO和WT小鼠CNS中的炎性细胞浸润和脱髓鞘相似。突变小鼠和WT小鼠的CNS CD 4 +T细胞计数相同。突变小鼠和野生型小鼠CNS中Th 17和Treg细胞的比例以及CNS中IL-17和TGF-β mRNA的表达没有显著差异。这些发现表明，CCL 20/CCR 6介导的细胞迁移不一定是EAE发病所必需的，并且可能被其他趋化因子信号所补偿。
Multiple sclerosis is an autoimmune disease in which the immune system attacks the nerve myelin sheath. The balance between pathogenic Th17 cells and regulatory Treg cells, both of which express the chemokine receptor CCR6 is critical for determining disease activity. It has been postulated that CCL20, the cognate ligand of CCR6, produced by the blood-brain barrier attracts these immune cells to the central nervous system (CNS). However, the pathological phenotypes of the experimental model of multiple sclerosis in CCR6-knockout (KO) mice are inconclusive, while this has not been addressed in CCL20-KO mice.To address this, we generated CCL20-KO and CCR6-KO mice using the CRISPR/Cas9 system. Clinical phenotypes of experimental autoimmune encephalomyelitis (EAE) in the chronic phase were slightly exacerbated in both mutant mice relative to those in wild-type (WT) mice. Inflammatory cell infiltration and demyelination in the CNS were similar in the KO and WT mice. CNS CD4+T cell counts were the same for mutant and WT mice. The mutant and WT mice did not differ significantly in the proportions of Th17 and Treg cells in the CNS, or in IL-17 and TGF-β mRNA expression in the CNS.These findings suggest that CCL20/CCR6-mediated cell migration is not necessarily required for the onset of EAE, and may be compensated for by other chemokine signals.