Filaggrin-mutant (Flg<sup>ft/ft</sup> ) mice develop spontaneous skin inflammation accompanied by an increase in skin ILC2 numbers, IL-1β production, and other cytokines recapitulating human AD.
These results suggest that β-carotene reduces skin inflammation through the suppressed expression of inflammatory factors or the activity of MMPs as well as the promotion of filaggrin expression in AD-like skin.
We sought to determine the mechanisms through which skin injury, dysbiosis, and increased epidermal IL-1α and IL-1β levels contribute to development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice without the matted mutation (ft/ft mice).
Filaggrin (FLG) loss-of-function (LOF) variants are a major risk factor for the common inflammatory skin disease, atopic dermatitis (AD) and are often population-specific.
Interestingly, <i>Il17ra<sup>-/-</sup></i> mice without the filaggrin mutation also developed spontaneous progressive skin inflammation with eosinophilia, as well as increased levels of thymic stromal lymphopoietin (TSLP) and IL-5 in the skin.
The aim of this study was to investigate whether immune-mediated skin inflammation differs between severe atopic dermatitis patients with or without filaggrin mutation.
This view is supported by findings that mutations in filaggrin, a key structural epidermal barrier protein, cause the inflammatory skin disease AD, and that a loss of AJ components, namely epidermal p120 catenin or α-catenin results in skin inflammation.
This is the first observation that the compound, which increased FLG expression in human and murine keratinocytes, attenuated the development of AD-like skin inflammation in mice.
These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms.
Using two complementary approaches, we have investigated αE (CD103) in psoriasis-like skin inflammation of mice with transgenic epidermal expression of human TGFβ1: αE (CD103) was inhibited by function-blocking antibodies in vivo, and double-mutants with additional αE (CD103)-depletion were generated in two different genetic backgrounds.
Further studies revealed that inflammation severity correlated with switching TGFβ1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGFβ1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease.
We demonstrated that keratinocytic ablation of Ctip2 leads to atopic dermatitis (AD)-like skin inflammation, characterized by alopecia, pruritus and scaling, as well as extensive infiltration of immune cells including T lymphocytes, mast cells, and eosinophils.
We produced models of skin inflammation induced by imiquimod (IMQ) and IL-23 and tested the effect of inhibiting LAT1 (JPH203) and mammalian target of rapamycin (mTOR [rapamycin]).
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) acts through its receptor fibroblast growth factor inducible 14 (Fn14), and participates in skin inflammation.