マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2022/11
形態種別	学術論文
査読	査読あり
標題	Microbiota-independent spontaneous dermatitis associated with increased sebaceous lipid production in Tmem79-deficient mice
執筆形態	共著
掲載誌名	Journal of Investigative Dermatology
掲載区分	国外
出版社・発行元	ELSEVIER
巻・号・頁	142(11),pp.2864-2872
総ページ数	9
著者・共著者	Ari Morimoto, Keitaro Fukuda, Yoshihiro Ito, Umi Tahara, Takashi Sasaki, Aiko Shiohama, Hiroshi Kawasaki, Eiryo Kawakami, Tatsuro Naganuma, Makoto Arita, Hiroyuki Sasaki, Haruhiko Koseki, Takeshi Matsui, Masayuki Amagai
概要	Sebaceous lipids comprise a large proportion of skin lipids and, as such, contribute to the skin barrier and stratum corneum hydration. Although reduced secretion and changes in the composition of sebaceous lipids are reported in atopic dermatitis (AD), their role in AD remains unclear. TMEM79 is a predisposing gene for AD. Tmem79-deficient mice develop spontaneous dermatitis in a biphasic pattern. The 1st-phase dermatitis is unique, as it occurs independent of microbiota status, whereas the 2nd-phase dermatitis is microbiota-dependent. In this study, we sought to identify key factors mediating the development of 1st-phase dermatitis. Structural analysis showed sebaceous gland hyperplasia started from 1st-phase dermatitis. Longitudinal RNA-sequencing analysis revealed significant activation of fatty acid lipid-metabolism pathways in 1st-phase dermatitis, whereas Th17-based immune response genes were highly expressed in 2nd-phase dermatitis. Quantitative reverse transcription polymerase chain reaction analysis revealed that genes involved in fatty acid elongation and sebocyte differentiation were upregulated in 1st-phase dermatitis. The results of thin-layer chromatography supported these findings with an increased abundance of wax esters, cholesterol esters, and fatty alcohols in hair lipids. Further gas chromatography-tandem mass spectrometry analysis showed an increase in total fatty acid production, including elongated C20-24 saturated and C18-24 mono-unsaturated fatty acids. Collectively, these results suggest that aberrant production of sebaceous long-chain fatty acids is associated with microbiota-independent dermatitis. Further investigation of Tmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.