气候变化领域集成服务门户(CCPortal): CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity

CCPortal

DOI	10.1073/pnas.2014492118
	CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity
	Manouchehri N.; Hussain R.Z.; Cravens P.D.; Esaulova E.; Artyomov M.N.; Edelson B.T.; Wu G.F.; Cross A.H.; Doelger R.; Loof N.; Eagar T.N.; Forsthuber T.G.; Calvier L.; Herz J.; Stüve O.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Natalizumab, a humanized monoclonal antibody (mAb) against α4- integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4- integrin in CD11c+ cells should curtail their migration to the central nervous system (CNS) and ameliorate experimental autoimmune encephalomyelitis (EAE). We generated CD11c.Cre+/-ITGA4fl/fl C57BL/6 mice to selectively delete α4-integrin in CD11c+ cells. Active immunization and adoptive transfer EAE models were employed and compared with WT controls. Multiparameter flow cytometry was utilized to immunophenotype leukocyte subsets. Single-cell RNA sequencing was used to profile individual cells. α4-Integrin expression by CD11c+ cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre+/-ITGA4fl/fl mice. In active EAE, a delayed disease onset was observed in CD11c.Cre+/-ITGA4fl/fl mice, during which CD11c+CD88+ cells were sequestered in the blood. Upon clinical EAE onset, CD11c+CD88+ cells appeared in the CNS and expressed CD317+. In adoptive transfer experiments, CD11c.Cre+/-ITGA4fl/fl mice had ameliorated clinical disease phenotype associated with significantly diminished numbers of CNS CD11c+CD88+CD317+ cells. In human cerebrospinal fluid from subjects with neuroinflammation, microglia-like cells display coincident expression of ITGAX (CD11c), C5AR1 (CD88), and BST2 (CD317). In mice, we show that only activated, but not naïve microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery in mice. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biomarker; CD317; EAE; Multiple sclerosis; Myeloid cells
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/180001
作者单位	Department of Neurology and Neurotherapeutics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, United States; Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO 63110, United States; Department of Neurology, Washington University, School of Medicine, St. Louis, MO 63110, United States; The Moody Foundation Flow Cytometry Facility, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, United States; Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States; Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, United States; Center for Translational Neurodegeneration Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390, United States; Department of Neuroscience, University of ...
推荐引用方式 GB/T 7714	Manouchehri N.,Hussain R.Z.,Cravens P.D.,et al. CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity[J],2021,118(14).
APA	Manouchehri N..,Hussain R.Z..,Cravens P.D..,Esaulova E..,Artyomov M.N..,...&Stüve O..(2021).CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Manouchehri N.,et al."CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).