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Cathepsin S Developes Chronic Atopic Dermatitis in Mice
Atopic dermatitis (AD) is a chronically relapsing, non‐contagious pruritic skin disease with two phases: acute and chronic. Previous studies have shown that cathepsin S (CTSS) is a cysteine protease linked to inflammatory processes, including atherosclerosis and asthma. The possibility that this or other cysteine proteases might evoke itch or be part of a classical ligand‐receptor signaling cascade has not been considered previously. Recently, CTSS was known as a ligand for proteinase‐activated receptor 2 (PAR2) associated with itching. In the present study, we showed that CTSS‐overexpressing transgenic (TG) mice spontaneously developed a skin disorder similar to chronic AD under conventional conditions. This study suggest that CTSS overexpression triggers PAR2 activation in dendritic cells (DCs), resulting in promotion of CD4+ differentiation involved in MHC class II expression. In addition, we investigated mast cells and macrophages and found significantly higher mean levels of T‐helper type 1 (Th1) cell‐associated cytokines than of T‐helper type 2 (Th2) cell‐associated cytokines in CTSS‐overexpressing TG mice. These results suggest that increasing of PAR2 expression in DCs mediated by CTSS overexpression induces scratching behavior and Th 1 cell‐associated cytokines, and can trigger chronic AD symtoms.
