AUTHOR=Chu Howard , Kim Su Min , Zhang KeLun , Wu Zhexue , Lee Hemin , Kim Ji Hye , Kim Hye Li , Kim Yu Ri , Kim Seo Hyeong , Kim Wan Jin , Lee Yang Won , Lee Kwang Hoon , Liu Kwang-Hyeon , Park Chang Ook 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1114321

DOI=10.3389/fimmu.2023.1114321

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction &amp; objectives</title><p>Head 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 <italic>Malassezia furfur</italic>.</p></sec><sec><title>Materials and methods</title><p>To identify the effect of the sensitization status of <italic>M. furfur</italic> on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of <italic>M. furfur</italic>, human keratinocytes and dermal endothelial cells were cultured with <italic>M. furfur</italic> 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 <italic>M. furfur</italic> 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.</p></sec><sec><title>Results</title><p>Increased sensitization to <italic>M. furfur</italic> was observed in patients with HND. Additionally, sensitization to <italic>M. furfur</italic> was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with <italic>M. furfur</italic> produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/<italic>M. furfur</italic> co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-β, TNF-α, and IL-1β levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, <italic>M. furfur</italic> growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including <italic>Cutibacterium acnes</italic>, were not inhibited.</p></sec><sec><title>Conclusions</title><p>Under decreased levels of ceramide in AD patients with HND, <italic>M. furfur</italic> 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.</p></sec>