气候变化领域集成服务门户(CCPortal): Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis

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DOI	10.1073/pnas.2017213118
	Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis
	Khaw Y.M.; Tierney A.; Cunningham C.; Soto-Díaz K.; Kang E.; Steelman A.J.; Inoue M.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4+ T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4+ T cells in white matter, gray matter-infiltrated CD4+ T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4+ T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4+T cell into the gray matter to induce neuronal damage. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Astrocyte; Dendritic spine loss; Gray matter; Multiple sclerosis; T cell migration
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180549
作者单位	Department of Comparative Biosciences, University of Illinois at Urbana–Champaign, Urbana, IL 61802, United States; Neuroscience Program, University of Illinois at Urbana–Champaign, Urbana, IL 61801, United States; School of Molecular and Cell Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801, United States; Department of Animal Sciences, College of Agricultural, Consumer, and Environmental Sciences, University of Illinois Urbana–Champaign, Urbana, IL 61801, United States; Division of Nutritional Sciences, University of Illinois Urbana–Champaign, Urbana, IL 61801, United States
推荐引用方式 GB/T 7714	Khaw Y.M.,Tierney A.,Cunningham C.,et al. Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis[J],2021,118(8).
APA	Khaw Y.M..,Tierney A..,Cunningham C..,Soto-Díaz K..,Kang E..,...&Inoue M..(2021).Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Khaw Y.M.,et al."Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).