Eosinophil-derived interferon-γ drives transmembrane protein 119-induced new bone formation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other. METHODS: We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone-forming activity of interferon-γ (IFN-γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN-γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin-4-eosinophil-IFN-γ axis and the effect of dupilumab were investigated in Eol-1 cells. RESULTS: We observed elevated IFN-γ levels and eosinophils in the nasal fluid and predominantly eosinophil-derived IFN-γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone-forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN-γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN-γ secretion by IL4-stimulated Eol-1 cells. CONCLUSION: Eosinophil-derived IFN-γ promotes the bone-forming activities of sinus bone cells via the STAT1-TMEM119 signaling pathway. Interleukin-4-eosinophil-IFN-γ axis may be crucial for TMEM119-mediated new bone formation in CRSwNP.

Working memory processing of facial images in schizophrenia: fMRI investigation.

Impaired processing of facial information is one of the broad ranges of cognitive deficits seen in patients with schizophrenia. This study aimed to elucidate the differences in brain activities involved in the process of facial working memory (images of neutral faces as mnemonic content) between schizophrenic patients and healthy comparison subjects using functional magnetic resonance imaging (fMRI). Group comparison analysis revealed aberrant activities from the patient group in several cortical areas, including the left fusiform gyrus, right superior frontal gyrus, bilateral middle frontal gyri/insula, and left middle temporal gyrus. A decreased level of activity in the left fusiform gyrus, along with performance reduction, implicates abnormal processing of facial information in schizophrenia.