Project description:BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in 2 maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic 3 mutations in Junctional Epidermolysis Bullosa (JEB) or autoantibody insult in Bullous Pemphigoid 4 (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 5 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-6 dysfunctional mouse strain and found that mice lacking functional BP180 (termed ΔNC16A) 7 developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin 8 barrier, infiltrating immune cells, elevated serum IgE levels and increased expression of thymic 9 stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but 10 dependent on increased expression of TSLP by keratinocytes. Our data provide the first direct 11 evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and 12 BP180 dysfunction leads to a TSLP mediated itch.
Project description:We conducted RNA sequencing analysis on skin tissues obtained from spontaneous inflammatory skin lesions in keratinocyte-specific Mettl3 knockout (K14CreERT2;Mettl3fl/fl) mice and their controls (Mettl3fl/fl). In brief, we observed spontaneous skin inflammation in the tail of K14CreERT2;Mettl3fl/fl mice 2-3 weeks following tamoxifen injection. The objective of this study was to investigate the impact and underlying mechanism of Mettl3 in epidermal keratinocytes regarding skin inflammation
Project description:This SuperSeries is composed of the following subset Series: GSE12248: Genetic architecture of murine skin inflammation and tumor susceptibility GSE21247: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (carcinomas) GSE21263: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas) GSE26273: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (aCGH) Refer to individual Series
Project description:To find which signaling is activated in chronic inflammation, we tried to induce chronic skin and pancreas inflammation compared to normal skin and pancreas.
Project description:Strong inhibition of NF-kB signaling in the epidermis results in spontaneous skin inflammation in mice and men. Since there is evidence for linkage between polymorphisms within the NF-kB signaling pathway and human inflammatory skin phenotypes, we asked whether partial functional inhibition of NF-kB signaling in epidermal keratinocytes can modulate clinically relevant skin inflammation. We therefore mutated rela specifically in the epidermis of mice (RelAE-MUT mice). These mice show no inflammatory phenotype. Induction of contact allergy, but not croton oil induced irritant dermatitis, resulted in stronger ear swelling and increased epidermal thickness in RelAE-MUT mice. Both contact allergen and croton oil treatment led to increase expression of calgranulins A and B (S100A8/ A9) in RelAE-MUT mice. Epidermal hyperproliferation in RelAE-MUT mice was non-cell autonomous since cultured primary epidermal keratinocytes from RelAE-MUT mice showed reduced proliferation compared to controls. These results demonstrate that epidermal RelA specifically regulates DTH-induced skin inflammation. In addition, we here describe an essential but non- specific function of RelA in the protection of epidermal keratinocytes from apoptosis. Our study identifies new functions of NF-kB signaling in the epidermis and corroborates a specific role of epidermal keratinocytes in the regulation of skin inflammation