Interleukin-34 restores blood-brain barrier integrity by upregulating tight junction proteins in endothelial cells

白细胞介素-34 通过上调内皮细胞紧密连接蛋白恢复血脑屏障的完整性

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作者:Shijie Jin, Yoshifumi Sonobe, Jun Kawanokuchi, Hiroshi Horiuchi, Yi Cheng, Yue Wang, Tetsuya Mizuno, Hideyuki Takeuchi, Akio Suzumura

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.

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