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Publication : Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice.

First Author  Morimoto A Year  2022
Journal  J Invest Dermatol PubMed ID  35752300
Mgi Jnum  J:327617 Mgi Id  MGI:7329629
Doi  10.1016/j.jid.2022.06.003 Citation  Morimoto A, et al. (2022) Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice. J Invest Dermatol
abstractText  TMEM79 is 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 17based 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 of Tmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.
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