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

Interdependence of Sebaceous Lipids and the Microbiome in Atopic Dermatitis

“…D ysfunction of the skin barrier, immune system, and microbiome all occur in atopic dermatitis (AD), but a single cause for this disease has not been clearly identified for all patients. Evidence supporting that AD is a multistep process that can involve lipid synthesis has been provided in a recent publication by Morimoto et al (2022). In Tmem79 -/mice used in this study, previous work of Ito et al (2021) showed that skin inflammation occurs in a biphasic pattern, with a first phase of dermatitis that occurs independently of the microbiota and a second phase that is microbiota dependent.…”

“…In Tmem79 -/mice used in this study, previous work of Ito et al (2021) showed that skin inflammation occurs in a biphasic pattern, with a first phase of dermatitis that occurs independently of the microbiota and a second phase that is microbiota dependent. In their study, Morimoto et al (2022) now show that a deletion of Tmem79 first results in abnormalities in lipid synthesis sufficient to trigger dermatitis, although the microbiome is required to trigger the final development of the disease (Figure 1).…”

“…Because mutation in Flg or Tmem79 can occur in the human population, Morimoto et al (2022) use Tmem79 À/À mice to investigate the factors that could help to understand AD. They show that these mice have hyperplasia of the sebaceous gland, and through RNA sequencing, they highlight an upregulation of fatty acid (FA) genes and sebocyte differentiation genes in chin skin.…”

Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice

“…In regard to TRPV3's function, TMEM79 is a putative five-pass transmembrane protein sharing similar dermal functions to TRPV3, including high expression in skin keratinocytes and involvement in itching or skin barrier formation. In this study, we found that TMEM79 reduced TRPV3mediated activities via protein-protein interactions [24][25][26][27][28] . Moreover, TMEM79-knockout mice rapidly responded to warmer temperatures in a thermal gradient, which is likely attributed to the increased levels of TRPV3.…”

Unlocking the therapeutic potential of TRPV3: Insights into thermosensation, channel modulation, and skin homeostasis involving TRPV3

“…Indeed, the skin of TMEM79 KO mice has an altered composition of fatty acids including long-chain to very long-chain fatty acids such as C18:1 (cis-9) oleic acid, ω6 polyunsaturated fatty acid C18:2 linoleic acid, C20:0 arachidic acid, C20:1 (cis-11) gondoic acid, C22:0 behenic acid, C22:1 (cis-13) erucic acid, C24:0 lignoceric acid, and C24:1 (cis-15) nervonic acid. [107] Importantly, TRPV3 function is potentiated by cholesterol and multiple fatty acids including oleic and linoleic acids that could indicate that the dermal dysfunction of TMEM79-deficient mice results in part from elevated TRPV3 activity that occurs when lipid production is increased. [59] Both PIP 2 depletion and cholesterol sensitize TRPV3 leading to activation of TRPV3 at lower temperatures, [60,61] suggesting that the preference of TMEM79 KO mice for elevated temperatures results in part from changes in lipid composition.…”