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Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation

 Howard Chu  ;  Su Min Kim  ;  KeLun Zhang  ;  Zhexue Wu  ;  Hemin Lee  ;  Ji Hye Kim  ;  Hye Li Kim  ;  Yu Ri Kim  ;  Seo Hyeong Kim  ;  Wan Jin Kim  ;  Yang Won Lee  ;  Kwang Hoon Lee  ;  Kwang-Hyeon Liu  ;  Chang Ook Park 
 FRONTIERS IN IMMUNOLOGY, Vol.14 : 1114321, 2023-02 
Journal Title
Issue Date
Ceramides ; Cytokines ; Dermatitis, Atopic* ; Endothelial Cells ; Humans ; Interleukin-4 ; Lipids ; Malassezia* / physiology
LC-MS/MS ; Malassezia ; atopic dermatitis ; ceramide ; head and neck dermatitis ; lipid analysis ; red face syndrome
Introduction & objectivesHead and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur. Materials and methodsTo identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry. ResultsIncreased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-beta, TNF-alpha, and IL-1 beta levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited. ConclusionsUnder decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Chu, Howard(곡원호)
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
Lee, Kwang Hoon(이광훈)
Lee, Hemin(이혜민)
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