Dataset Information


Inner ear supporting cells are organized tissue-resident macrophages arranged like cobblestones.

ABSTRACT: Sensorineural hearing loss (SHL) is a relatively common disease, and studies have suggested viral infection as a major cause. In the inner ear, the blood-labyrinthine barrier prevents access of the peripheral immune system; therefore, the immune system remains poorly understood. Here we found that cochlear accessory supporting cells (SCs), which are anchored by tight junctions, are organized tissue-resident macrophages. Virus-infected supporting cells change into activated macrophages and protect audiosensory receptor hair cells (HCs) against virus infection by producing interferon (IFN)-α/β. Moreover, we also observed bacterial phagocytosis by SCs. However, tumour necrosis factor-related apoptosis-inducing ligand (Trail), produced by virus-infected SCs, induced sensory hair loss and HC death by necroptosis. Notably, corticosteroid, the only effective drug for SHL, inhibited the virus-induced macrophage change of SCs. These results revealed an inner ear immune system, and suggest a possible mechanism for virus-induced SHL. Overall design: To understand the mechanism of virus- and LPS-induced macrophage change of cochlear supporting cells, we analysed the mRNA expression profiles of inner ear sensory epithelium in the absence of and presence of these stimulations. The RNeasy Micro Kit (Qiagen) was used to extract total RNA from three cochlear sensory epithelia. For microarray, total RNA was extracted from nine mock explants, nine explants treated with 1000 ng/ml LPS for 16 h, or fourteen explants infected with TMEV (Theiler’s murine encephalomyelitis virus) for 16 h using the RNeasy Micro Kit. TMEV infection for 16 h induced cochlear cell death in hair cells and supporting cells, so a greater number of TMEV-infected cochleae were needed compared with mock and LPS-treated cochleae to equalize the amount of total RNA. Filgen (the company for biological technical service) performed the microarray analysis using GeneChip Mouse Gene 2.0 ST Array (Affymetrix).

INSTRUMENT(S): [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]

SUBMITTER: Nobuyuki Tanaka  

PROVIDER: GSE89556 | GEO | 2016-12-10



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