title: Microglia activity modulated by T cell Ig and mucin domain protein 3 (Tim-3).
abstract: Microglia are the main innate immune cells in the central nervous system that are actively involved in maintaining brain homeostasis and diseases. T cell Ig and mucin domain protein 3 (Tim-3) plays critical roles in both the adaptive and the innate immune system and is an emerging therapeutic target for treatment of various disorders. In the brain Tim-3 is specifically expressed on microglia but its functional role is unclear. Here, we showed that Tim-3 was up-regulated on microglia by ATP or LPS stimulation. Tim-3 activation with antibodies increased microglia expression of TGF-β, TNF-α and IL-1β. Blocking of Tim-3 with antibodies decreased the microglial phagocytosis of apoptotic neurons. Tim-3 blocking alleviated the detrimental effect of microglia on neurons and promoted NG2 cell differentiation in co-cultures. Finally, MAPKs namely ERK1/2 and JNK proteins were phosphorylated upon Tim-3 activation in microglia. Data indicated that Tim-3 modulates microglia activity and regulates the interaction of microglia-neural cells.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China; The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China.
authors.forename: Xin-li
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Qin
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China.
authors.forename: Hai-jun
authors.initials: HJ
authors.lastname: Qian
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, PR China. Electronic address: yinerwang@zju.edu.cn.
authors.forename: Yiner
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D000072597:Hepatitis A Virus Cellular Receptor 2; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D011991:Receptors, Virus / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000906:Antibodies; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011991:Receptors, Virus; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4
keywords: MAPK; Microglia; NF-κB; NG2 cell; Neuron; Tim-3