BP180 dysfunction triggers spontaneous skin inflammation in mice

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. Total six samples, three controls (WT) and three test (KO). All of the sample are the RNA extracted from fresh mouse skin tissue; from three WT mice and three KO mice. Age and sex are matched.