Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease

doi:10.3389/fimmu.2018.00513

	Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease
	Dey, Adwitia 1; Allen, Joselyn N.1; Fraser, James W.1; Snyder, Lindsay M.1; Tian, Yuan 1,2; Zhang, Limin 1; Paulson, Robert F.1; Patterson, Andrew 1; Cantorna, Margherita T.1; Hankey-Giblin, Pamela A.1
刊名	FRONTIERS IN IMMUNOLOGY
	2018-03-19
卷号	9
关键词	Neuroinflammation Tyrosine Kinase Macrophage Experimental Autoimmune Encephalomyelitis Diet-induced Obesity Central Nervous System
ISSN号	1664-3224
DOI	10.3389/fimmu.2018.00513
文献子类	Article
英文摘要	Neurodegeneration is a critical problem in aging populations and is characterized by severe central nervous system (CNS) inflammation. Macrophages closely regulate inflammation in the CNS and periphery by taking on different activation states. The source of inflammation in many neurodegenerative diseases has been preliminarily linked to a decrease in the CNS M2 macrophage population and a subsequent increase in M1-mediated neuroinflammation. The Recepteur D'Origine Nantais (Ron) is a receptor tyrosine kinase expressed on tissue-resident macrophages including microglia. Activation of Ron by its ligand, macrophage-stimulating protein, attenuates obesity-mediated inflammation in the periphery. An in vivo deletion of the ligand binding domain of Ron (Ron(-/-)) promotes inflammatory (M1) and limits a reparative (M2) macrophage activation. However, whether or not this response influences CNS inflammation has not been determined. In this study, we demonstrate that in homeostasis Ron(-/-) mice developed an inflammatory CNS niche with increased tissue expression of M1-associated markers when compared to age-matched wild-type (WT) mice. Baseline metabolic analysis of CNS tissue indicates exacerbated levels of metabolic stress in Ron(-/-) CNS. In a disease model of multiple sclerosis, experimental autoimmune encephalomyelitis, Ron(-/-)mice exhibit higher disease severity when compared to WT mice associated with increased CNS tissue inflammation. In a model of diet-induced obesity (DIO), Ron(-/-)mice exhibit exacerbated CNS inflammation with decreased expression of the M2 marker Arginase-1 (Arg-1) and a robust increase in M1 markers compared to WT mice following 27 weeks of DIO. Collectively, these results illustrate that activation of Ron in the CNS could be a potential therapeutic approach to treating various grades of CNS inflammation underlying neurodegeneration.
WOS关键词	MACROPHAGE-STIMULATING PROTEIN ; PERITONEAL-MACROPHAGES ; NEUROTROPHIC FACTOR ; INNATE IMMUNITY ; IFN-GAMMA ; BRAIN ; ACTIVATION ; NEURODEGENERATION ; MICE ; NEUROINFLAMMATION
WOS研究方向	Immunology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000427733100001
资助机构	USDA-NIFA Hatch project(4581) ; USDA-NIFA Hatch project(4581) ; Department of VBS ; Department of VBS ; American Association of Immunologists Careers Fellowship ; American Association of Immunologists Careers Fellowship ; (NRSA-5 T32 GM 108563-3) ; (NRSA-5 T32 GM 108563-3) ; (T32: 2T32AI074551-06) ; (T32: 2T32AI074551-06) ; (R01 DK080040) ; (R01 DK080040) ; USDA-NIFA Hatch project(4581) ; USDA-NIFA Hatch project(4581) ; Department of VBS ; Department of VBS ; American Association of Immunologists Careers Fellowship ; American Association of Immunologists Careers Fellowship ; (NRSA-5 T32 GM 108563-3) ; (NRSA-5 T32 GM 108563-3) ; (T32: 2T32AI074551-06) ; (T32: 2T32AI074551-06) ; (R01 DK080040) ; (R01 DK080040) ; USDA-NIFA Hatch project(4581) ; USDA-NIFA Hatch project(4581) ; Department of VBS ; Department of VBS ; American Association of Immunologists Careers Fellowship ; American Association of Immunologists Careers Fellowship ; (NRSA-5 T32 GM 108563-3) ; (NRSA-5 T32 GM 108563-3) ; (T32: 2T32AI074551-06) ; (T32: 2T32AI074551-06) ; (R01 DK080040) ; (R01 DK080040) ; USDA-NIFA Hatch project(4581) ; USDA-NIFA Hatch project(4581) ; Department of VBS ; Department of VBS ; American Association of Immunologists Careers Fellowship ; American Association of Immunologists Careers Fellowship ; (NRSA-5 T32 GM 108563-3) ; (NRSA-5 T32 GM 108563-3) ; (T32: 2T32AI074551-06) ; (T32: 2T32AI074551-06) ; (R01 DK080040) ; (R01 DK080040)
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/12898]
专题	中国科学院武汉物理与数学研究所
通讯作者	Hankey-Giblin, Pamela A.
作者单位	1.Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA 2.Univ Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, CAS Key Lab Magnet Resonance Biol Syst, Wuhan, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Dey, Adwitia,Allen, Joselyn N.,Fraser, James W.,et al. Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease[J]. FRONTIERS IN IMMUNOLOGY,2018,9.
APA	Dey, Adwitia.,Allen, Joselyn N..,Fraser, James W..,Snyder, Lindsay M..,Tian, Yuan.,...&Hankey-Giblin, Pamela A..(2018).Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease.FRONTIERS IN IMMUNOLOGY,9.
MLA	Dey, Adwitia,et al."Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease".FRONTIERS IN IMMUNOLOGY 9(2018).