自交轴蛋白
溶血磷脂酸
生物
免疫系统
免疫学
过继性细胞移植
多发性硬化
髓鞘少突胶质细胞糖蛋白
T细胞
实验性自身免疫性脑脊髓炎
细胞生物学
受体
生物化学
作者
Cora L. Petersen-Cherubini,Shawn P. Murphy,Matthew K. Xin,Yue Liu,Joshua L. Deffenbaugh,Ishrat Jahan,Christina N. Rau,Yuhong Yang,Amy E. Lovett-Racke
标识
DOI:10.1002/eji.202350561
摘要
Abstract Multiple sclerosis (MS) is an immune‐mediated inflammatory disease of the CNS. A defining characteristic of MS is the ability of autoreactive T lymphocytes to cross the blood–brain barrier and mediate inflammation within the CNS. Previous work from our lab found the gene Enpp2 to be highly upregulated in murine encephalitogenic T cells. Enpp2 encodes for the protein autotaxin, a secreted glycoprotein that catalyzes the production of lysophosphatidic acid and promotes transendothelial migration of T cells from the bloodstream into the lymphatic system. The present study sought to characterize autotaxin expression in T cells during CNS autoimmune disease and determine its potential therapeutic value. Myelin‐activated CD4 T cells upregulated expression of autotaxin in vitro, and ex vivo analysis of CNS‐infiltrating CD4 T cells showed significantly higher autotaxin expression compared with cells from healthy mice. In addition, inhibiting autotaxin in myelin‐specific T cells reduced their encephalitogenicity in adoptive transfer studies and decreased in vitro cell motility. Importantly, using two mouse models of MS, treatment with an autotaxin inhibitor ameliorated EAE severity, decreased the number of CNS infiltrating T and B cells, and suppressed relapses, suggesting autotaxin may be a promising therapeutic target in the treatment of MS.
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