Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice
Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice
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Tmem79 缺陷小鼠皮脂分泌增加与微生物群无关的自发性皮炎
DOI：
10.1016/j.jid.2022.06.003
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发表时间：
2022
影响因子：
6.5
通讯作者：
Amagai Masayuki
中科院分区：
文献类型：
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作者：
Morimoto Ari;Fukuda Keitaro;Ito Yoshihiro;Tahara Umi;Sasaki Takashi;Shiohama Aiko;Kawasaki Hiroshi;Kawakami Eiryo;Naganuma Tatsuro;Arita Makoto;Sasaki Hiroyuki;Koseki Haruhiko;Matsui Takeshi;Amagai Masayuki
TMEM 79是特应性皮炎的易感基因，TMEM 79缺陷小鼠发生自发性皮炎的模式为双相型。第一阶段皮炎是独特的，因为它的发生与微生物群状态无关，而第二阶段皮炎是微生物群依赖性的。在这项研究中，我们试图确定介导第一阶段皮炎发展的关键因素。结构分析表明，皮脂腺增生始于第一期皮炎。纵向RNA测序分析显示，脂肪酸脂质代谢途径在第一阶段皮炎的显着激活，而辅助性T细胞17 β为基础的免疫应答基因在第二阶段皮炎高度表达。定量RT-PCR分析显示，参与脂肪酸延伸和皮脂细胞分化的基因在第一阶段皮炎中上调。薄层层析的结果支持这些发现与增加丰富的蜡酯，胆固醇酯，脂肪醇在头发脂质。进一步的气相色谱-串联质谱分析显示总脂肪酸产量增加，包括延长的C20-24饱和脂肪酸和C18-24单不饱和脂肪酸。总的来说，这些结果表明，皮脂长链脂肪酸的异常产生与微生物群非依赖性皮炎有关。对Tmem 79缺陷小鼠的进一步研究可能会阐明某些脂肪酸在皮炎中的作用。
TMEM79is a predisposing gene for atopic dermatitis.Tmem79-deficient mice develop spontaneous dermatitis in a biphasic pattern. The first-phase dermatitis is unique because it occurs independent of microbiota status, whereas the second-phase dermatitis is microbiota dependent. In this study, we sought to identify the key factors mediating the development of first-phase dermatitis. Structural analysis showed that sebaceous gland hyperplasia started from first-phase dermatitis. Longitudinal RNA sequencing analysis revealed significant activation of fatty acid lipid metabolism pathways in first-phase dermatitis, whereas T helper 17‒based immune response genes were highly expressed in second-phase dermatitis. Quantitative RT-PCR analysis revealed that genes involved in fatty acid elongation and sebocyte differentiation were upregulated in first-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 that of elongated C20–24 saturated and C18–24 monounsaturated fatty acids. Collectively, these results suggest that aberrant production of sebaceous long-chain fatty acids is associated with microbiota-independent dermatitis. Further investigation ofTmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.