气候变化领域集成服务门户(CCPortal): Pericytes regulate vascular immune homeostasis in the CNS

CCPortal

DOI	10.1073/pnas.2016587118
	Pericytes regulate vascular immune homeostasis in the CNS
	Török O.; Schreiner B.; Schaffenrath J.; Tsai H.-C.; Maheshwari U.; Stifter S.A.; Welsh C.; Amorim A.; Sridhar S.; Utz S.G.; Mildenberger W.; Nassiri S.; Delorenzi M.; Aguzzi A.; Han M.H.; Greter M.; Becher B.; Keller A.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood–brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfbret/ret), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfbret/ret mice inversely correlates with vessel pericyte coverage. Upon induction of experimental autoimmune encephalomyelitis (EAE), pericyte-deficient mice die of severe atypical EAE, which can be reversed with fingolimod, indicating that the mortality is due to the massive influx of immune cells into the brain. Additionally, administration of anti-VCAM-1 and anti–ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfbret/ret mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation. Furthermore, we show that the presence of myelin peptide-specific peripheral T cells in Pdgfbret/ret;2D2tg mice leads to the development of spontaneous neurological symptoms paralleled by the massive influx of leukocytes into the brain. These findings indicate that intrinsic changes within brain vasculature can promote the development of a neuroinflammatory disorder. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoimmune neuroinflammation; Blood–brain barrier; Leukocyte trafficking; MOG35–55–specific T cell receptor; Pericyte
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/180425
作者单位	Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zürich, Zürich University, Zürich, 8091, Switzerland; Neuroscience Center Zürich, University of Zürich, ETH Zürich, Zürich, 8057, Switzerland; Institute of Experimental Immunology, University of Zürich, Zürich, 8057, Switzerland; Department of Neurology, University Hospital Zurich, Zürich, 8091, Switzerland; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, United States; Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Institute of Neuropathology, University Hospital Zürich, Zürich, 8091, Switzerland
推荐引用方式 GB/T 7714	Török O.,Schreiner B.,Schaffenrath J.,et al. Pericytes regulate vascular immune homeostasis in the CNS[J],2021,118(10).
APA	Török O..,Schreiner B..,Schaffenrath J..,Tsai H.-C..,Maheshwari U..,...&Keller A..(2021).Pericytes regulate vascular immune homeostasis in the CNS.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Török O.,et al."Pericytes regulate vascular immune homeostasis in the CNS".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).