A skin isolate ofnegates theinduced release of type 2 cytokines from keratinocytes.

Abstract

second immunoglobulin-binding protein (Sbi) is a unique type 2-promoting virulence factor that induces IL-33 and thymic stromal lymphopoietin (TSLP) release. This mechanism is essential for the development of-induced eczema in the widely used NC/Tnd mouse model of human atopic dermatitis (AD). Microbiome shifts in AD suggest that microbiota could modulate the disease. We therefore sought to identify skin bacteria that attenuateinduced IL-33/TSLP release from keratinocytes.was unique among skin isolates in its ability to negate cytokine induction. The bioactive factor responsible was identified using fractionation, LC-MS and recombinant proteins, as the serine protease "PA domain protein" (PADP). Immunoblotting and ELISA confirmed Sbi and IL-33 degradation by PADP. This was not observed with thetype strain which contains a frame shift mutation within the PADP active site. These data provide new insights into the role of skin microbiota in AD and highlights their potential as topical therapeutics.