title: Interleukin-34 restores blood-brain barrier integrity by upregulating tight junction proteins in endothelial cells.
abstract: Interleukin-34 (IL-34) is a newly discovered cytokine as an additional ligand for colony stimulating factor-1 receptor (CSF1R), and its functions are expected to overlap with colony stimulating factor-1/macrophage-colony stimulating factor. We have previously shown that the IL-34 is primarily produced by neurons in the central nervous system (CNS) and induces proliferation and neuroprotective properties of microglia which express CSF1R. However, the functions of IL-34 in the CNS are still elucidative. Here we show that CNS capillary endothelial cells also express CSF1R. IL-34 protected blood-brain barrier integrity by restored expression levels of tight junction proteins, which were downregulated by pro-inflammatory cytokines. The novel function of IL-34 on the blood-brain barrier may give us a clue for new therapeutic strategies in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanokuchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horiuchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000378:metabolism; D002199:Capillary Permeability; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D062725:Tight Junction Proteins / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D007378:Interleukins; D062725:Tight Junction Proteins; C552364:interleukin-34, mouse