Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis.
Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Ji Heui
JH
Kim
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Korea.|Institute of Convergence Bio-Health, Dong-A University, Busan, Republic of Korea.
Go Eun
GE
Choi
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Bong-Jae
BJ
Lee
Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
Seog Woon
SW
Kwon
Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Seung-Hyo
SH
Lee
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Korea.|Cellular Dysfunction Research Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.|Department of Microbiology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Hun Sik
HS
Kim
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Yong Ju
YJ
Jang
D000328:Adult; D000368:Aged; D000818:Animals; D002908:Chronic Disease; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D015230:Prostaglandin D2 / Q000235:genetics*; D012852:Sinusitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D015230:Prostaglandin D2