Chondroitin sulfate N-acetylgalactosyltransferase-1 knockout shows milder phenotype in experimental autoimmune encephalomyelitis than in wild type
Chondroitin sulfate N-acetylgalactosyltransferase-1 knockout shows milder phenotype in experimental autoimmune encephalomyelitis than in wild type
复制标题
硫酸软骨素 N-乙酰半乳糖基转移酶-1 敲除在实验性自身免疫性脑脊髓炎中表现出比野生型更温和的表型
DOI：
10.1093/glycob/cwaa072
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发表时间：
2020
期刊：
影响因子：
4.3
通讯作者：
Kusunoki Susumu
中科院分区：
文献类型：
--
作者：
Inada Rino;Miyamoto Katsuichi;Tanaka Noriko;Moriguchi Kota;Kadomatsu Kenji;Takeuchi Kosei;Igarashi Michihiro;Kusunoki Susumu
蛋白多糖是中枢神经系统细胞外基质的主要成分之一。硫酸软骨素（CS）是一种糖胺聚糖（GAG），由主要的pg组成。与另一种GAG硫酸角蛋白（KS）类似，CS抑制轴突再生。然而，这些gag对神经免疫疾病致病性的影响尚不清楚。在这里，我们在缺乏CS n -乙酰半乳糖氨基转移酶-1 （CSGalNAcT1-KO）的小鼠中诱导了实验性自身免疫性脑脊髓炎（EAE）， CSGalNAcT1-KO是CS合成的重要酶。在我们的研究中，CSGalNAcT1-KO小鼠比野生型（WT）小鼠表现出更轻的EAE症状。抗原特异性淋巴细胞的召回反应表明，csgalnact1 - ko来源的淋巴细胞比wt来源的淋巴细胞具有更温和的细胞增殖反应。这些结果表明，CS对EAE的诱导阶段有一定的作用。我们之前在glcnac -6- o -硫转移酶KO （GlcNAc6ST-KO）和C6ST1-KO小鼠中进行了EAE实验，分别降低了KS和CS-C。与C6ST1-KO小鼠相比，CSGalNAcT1-KO小鼠的EAE与GlcNAc6ST-KO小鼠更相似。总之，不同的GAG糖链与EAE的严重或轻度表型相关，因此是包括多发性硬化症在内的神经免疫疾病的潜在新治疗靶点。
Proteoglycans (PGs) are one of the main components in the extracellular matrix of the central nervous system. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG), which is composed of major PGs. Similar to keratin sulfate (KS), another GAG, CS inhibits axon regeneration. However, the influence of these GAGs on the pathogenicity of neuroimmunological diseases is unclear. Here, we induced experimental autoimmune encephalomyelitis (EAE) in mice lacking CS N-acetylgalactosaminyltransferase-1 (CSGalNAcT1-KO), an important enzyme for CS synthesis. In our study, CSGalNAcT1-KO mice showed milder EAE symptoms than those in wild-type (WT) mice. The recall response of antigen-specific lymphocytes showed that CSGalNAcT1-KO-derived lymphocytes had a milder cell proliferation response than that in WT-derived lymphocytes. These results suggest that CS contributes toward the induction phase of EAE. We previously performed EAE experiments in GlcNAc-6-O-sulfotransferase KO (GlcNAc6ST-KO) and C6ST1-KO mice, which had reduced KS and reduced CS-C, respectively. EAE in CSGalNAcT1-KO mice was more similar to that in GlcNAc6ST-KO mice than in C6ST1-KO mice. In conclusion, the distinct GAG sugar chains are associated with severe or mild phenotypes of EAE and are therefore potential new therapeutic targets for neuroimmunological diseases, including multiple sclerosis.