APM OpenIR
Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease
Dey, Adwitia1; Allen, Joselyn N.1; Fraser, James W.1; Snyder, Lindsay M.1; Tian, Yuan1,2; Zhang, Limin1; Paulson, Robert F.1; Patterson, Andrew1; Cantorna, Margherita T.1; Hankey-Giblin, Pamela A.1
2018-03-19
Source PublicationFRONTIERS IN IMMUNOLOGY
ISSN1664-3224
Volume9
SubtypeArticle
AbstractNeurodegeneration 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.
KeywordNeuroinflammation Tyrosine Kinase Macrophage Experimental Autoimmune Encephalomyelitis Diet-induced Obesity Central Nervous System
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationUSDA-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)
DOI10.3389/fimmu.2018.00513
WOS KeywordMACROPHAGE-STIMULATING PROTEIN ; PERITONEAL-MACROPHAGES ; NEUROTROPHIC FACTOR ; INNATE IMMUNITY ; IFN-GAMMA ; BRAIN ; ACTIVATION ; NEURODEGENERATION ; MICE ; NEUROINFLAMMATION
Indexed BySCI
Language英语
Funding OrganizationUSDA-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)
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000427733100001
PublisherFRONTIERS MEDIA SA
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/12899
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorHankey-Giblin, Pamela A.
Affiliation1.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
Recommended Citation
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).
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