Autophagy deficiency in myeloid cells exacerbates eosinophilic inflammation in chronic rhinosinusitis
Authors: Hun Sik Kim
Yong Ju Jang
Ji-Yun Kim
Go Eun Choi
Do-Young Kang
Seung-Yong Yoon
Journal: Journal of Allergy and Clinical Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: Chronic rhinosinusitis; autophagy; eosinophil; macrophage; prostaglandin D(2).
Affiliations: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea; Institute of Convergence Bio-Health, Dong-A University, Busan, Korea., Alzheimer Disease Experts Lab (ADEL), Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea; Department of Brain Science, University of Ulsan College of Medicine, Seoul, Korea; Cellular Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea., Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea; Cellular Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea., Institute of Convergence Bio-Health, Dong-A University, Busan, Korea; Department of Nuclear Medicine, Dong-A University Medical Center, College of Medicine, Dong-A University, Busan, Korea., Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea; Cellular Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Microbiology, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: .

Abstract:  Background: Eosinophilic inflammation is a major pathologic feature of chronic rhinosinusitis (CRS) and is frequently associated with severe refractory disease. Prostaglandin (PG) D2 levels are increased in patients with CRS, and PGD2 is an important contributing factor to eosinophilic inflammation. Autophagy has a pleiotropic effect on immune responses and disease pathogenesis. Recent studies suggest the potential involvement of autophagy in patients with CRS and the PG pathway. Objective: We sought to investigate whether altered function of autophagy is associated with eosinophilic inflammation and dysregulated production of PGD2 in patients with CRS. Methods: We used myeloid cell-specific deletion of autophagy-related gene 7 (Atg7), which is vital for autophagy, and investigated the effects of impaired autophagy on eosinophilic inflammation in a murine model of eosinophilic chronic rhinosinusitis (ECRS). The effect of autophagy on PGD2 production and gene expression profiles associated with allergy and the PG pathway were assessed. Results: We found that impaired autophagy in myeloid cells aggravated eosinophilia, epithelial hyperplasia, and mucosal thickening in mice with ECRS. This aggravation was associated with gene expression profiles that favor eosinophilic inflammation, TH2 response, mast cell infiltration, and PGD2 dysregulation. Supporting this, PGD2 production was also increased significantly by impaired autophagy. Among other myeloid cells, macrophages were associated with autophagy deficiency, leading to increased IL-1Œ≤ levels. Macrophage depletion or blockade of IL-1 receptor led to alleviation of eosinophilic inflammation and sinonasal anatomic abnormalities associated with autophagy deficiency. Conclusion: Our results suggest that impaired autophagy in myeloid cells, particularly macrophages, has a causal role in eosinophilic inflammation and ECRS pathogenesis. 

Retracted: No

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 The PI is responsible for the research. However, PI words seem to be quite problematic, as it sounds like a nuance of assigning the responsibility of research to the first author. Please show a responsible attitude. ,