557 Microbiome controls mast cell differentiation in the skin

Commensal microbiota play important roles in the skin’s immune system. Originally from bone marrow, mast cell (MC) progenitors enter the skin and become mature in the surrounding microenvironment of skin. Previous studies demonstrate that murine MCs do not fully mature until 8 to 15 days after birth. We hypothesized that skin commensal bacteria and their products have important effects on MC maturation in the skin. Here we show that in skin, germ-free (GF) mice express low levels of stem cell factor (SCF), a critical MC differentiation factor, and their skin MCs are less mature. Immunofluorescence staining and FACS results revealed a smaller population of c-Kit positive MCs in the GF mice that can be normalized after being co-housed with conventional mice for 5 weeks to reconstitute their microbiome. Real time qPCR results of toluidine blue positive cells in the skin, collected by laser capture microdissection, showed that MCs in GF skin expressed lower levels of various MC markers including chymase, tryptase beta 2, MC protease 4, c-Kit, and cathelicidin antimicrobial peptide. Furthermore, compound 48/80, a known degranulation agent, induced less edema in the paws of GF mice than in those of conventional mice. We also found that lipoteichoic acid (a major constituent of the cell wall of Staphylococcus) promotes SCF production in keratinocytes through TLR2, which enhances the development of skin MCs. Our findings are important for the skin diseases involving MCs, such as atopic dermatitis or psoriasis, in which the change in the skin commensal microbiota has been proven to be part of their pathogenesis.