Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease
文献类型：期刊论文
| 作者 | Zhang, Limin1; Dey, Adwitia1; Allen, Joselyn N.1; Fraser, James W.1; Snyder, Lindsay M.1; Tian, Yuan1,2; Paulson, Robert F.1; Patterson, Andrew1; Cantorna, Margherita T.1; Hankey-Giblin, Pamela A.1 |
| 刊名 | FRONTIERS IN IMMUNOLOGY
 |
| 出版日期 | 2018-03-19 |
| 卷号 | 9页码:13 |
| 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 |
| 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. |
| 资助项目 | USDA-NIFA Hatch project[4581] ; Department of VBS ; American Association of Immunologists Careers Fellowship ; [NRSA-5 T32 GM 108563-3] ; [T32: 2T32AI074551-06] ; [R01 DK080040] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:000427733100001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/4812]  |
| 专题 | 中国科学院武汉植物园 |
| 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 | Zhang, Limin,Dey, Adwitia,Allen, Joselyn N.,et al. Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease[J]. FRONTIERS IN IMMUNOLOGY,2018,9:13. |
| APA | Zhang, Limin.,Dey, Adwitia.,Allen, Joselyn N..,Fraser, James W..,Snyder, Lindsay M..,...&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,9,13. |
| MLA | Zhang, Limin,et al."Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease".FRONTIERS IN IMMUNOLOGY 9(2018):13. |
入库方式： OAI收割
来源：武汉植物园
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