Microbiota-Independent Spontaneous Dermatitis Associated With Increased Sebaceous Lipid Production in Tmem79-Deficient Mice

J Invest Dermatol. 2022 Jun 22:S0022-202X(22)01588-3. doi: 10.1016/j.jid.2022.06.003. Online ahead of print.


TMEM79 is a predisposing gene for atopic dermatitis (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 that 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 that of 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.

PMID:35752300 | DOI:10.1016/j.jid.2022.06.003

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