title: Interferon-γ safeguards blood-brain barrier during experimental autoimmune encephalomyelitis.
abstract: The function of blood-brain barrier is often disrupted during the progression of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the molecular mechanism of blood-brain barrier modulation during neuroinflammation remains unclear. Herein, we show that the expression of interferon-γ (IFNγ) receptor on endothelial cells (ECs) protected mice from the brain inflammation during EAE. IFNγ stabilized the integrity of the cerebral endothelium and prevented the infiltration of leukocytes into the brain. Further analysis revealed that IFNγ increased the expression of tight junction proteins zonula occludens protein 1 and occludin, as well as membranous distribution of claudin-5, in brain ECs. Silencing claudin-5 abolished the IFNγ-mediated improvement of EC integrity. Taken together, our results show that IFNγ, a pleiotropic proinflammatory cytokine, stabilizes blood-brain barrier integrity and, therefore, prevents brain inflammation during EAE.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ni
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Guangdong Medical College, Zhanjiang, China; Leibniz Institute for Molecular Pharmacology, Berlin-Buch, Germany.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Qu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Deng
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Berlin-Buch, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Lorenz
authors.affiliation: Xinxiang Medical University, Xinxiang, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Yan
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Berlin-Buch, Germany.
authors.forename: Ingolf E
authors.initials: IE
authors.lastname: Blasig
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: zhihai@ibp.ac.cn.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology*; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D042787:Receptor, TIE-2 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062507:Claudin-5; C491511:Cldn5 protein, mouse; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma; D042787:Receptor, TIE-2; C079086:Tek protein, mouse