The Absence of a Microbiota Enhances TSLP Expression in Mice with Defective Skin Barrier but Does Not Affect the Severity of their Allergic Inflammation

Evidence is accumulating to suggest that our indigenous microbial communities (microbiota) may have a role in modulating allergic and immune disorders of the skin. To examine the link between the microbiota and atopic dermatitis (AD), we examined a mouse model of defective cutaneous barrier function with an AD-like disease due to loss of Notch signaling. Comparisons of conventionally raised and germ-free (GF) mice revealed a similar degree of allergic skin inflammation, systemic atopy, and airway hypersensitivity. GF mutant animals expressed significantly higher levels of thymic stromal lymphopoietin, a major proinflammatory cytokine released by skin with defective barrier function, resulting in a more severe B-lymphoproliferative disorder that persisted into adulthood. These findings suggest a role for the microbiota in ameliorating stress signals released by keratinocytes in response to perturbation in cutaneous barrier function.