582:
Skin microbiome regulates SCF level in Keratinocytes and defines mast cell maturation
Sunday, March 4, 2018: 3:00 PM
S220EF (Convention Center)
Anna Di Nardo, , , , ,
RATIONALE: Mast cell (MC) progenitors, from the blood, become mature in the dermal micro-environment. We hypothesized that skin commensal bacteria work together with normal human epidermal keratinocytes (NHEK) to retain and differentiate mast cells within the skin.

METHODS: We compared mast cells (MCs) obtained from the skin of germ free mice (GF) and compared them to specific pathogen free mice (SPF) and GF mice co-housed with SPF mice for 5 weeks in SPF facility

RESULTS: Skin GF-MCs were significantly less mature by FACS (p<0.01) and qPCR (p<0.05). MCs immaturity associated with reduced levels of stem cell factor (SCF), critical for MC survival. GF mice developed significantly less edema in the in vivo degranulation test, as measured by paw swelling after compound 48/80 injection. FACS staining revealed that there was 50% fewer c-Kit+ MCs in the GF mice which normalized when they were co-housed with SPF mice.

CONCLUSIONS:

Skin MCs isolated from GF mice are phenotypically immature and express reduced levels of the MC survival receptor, c-Kit per cell. These abnormalities reverted to normal when the GF mice co-housed with SPF mice. We hypothesize that mice that have a skin microbiome richer in gram positive bacteria (with more Lipoteichoic acid), would have keratinocytes that produce more SCF resulting in greater numbers of mature MCs. Our findings are important for the skin diseases involving MCs, such as atopic dermatitis, in which the change in the skin commensal microbiota strongly associates with disease activity.