MyD88 signaling in T regulatory cells by endogenous ligands dampens skin inflammation in filaggrin deficient mice

摘要

Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient flaky tail (Flgft/ft) mice develop spontaneous inflammatory skin lesion that wax and wane. We show that loss of MyD88 promotes the persistence of skin lesions inFlgft/ftmice and exaggerates their expression of the Th17-associated cytokinesIl7aandIl22. The development and persistence of skin lesions inFlgft/ftmice was independent of the microbiota. MyD88-mediated signals are shown to be important for the accumulation of T regulatory cells (Tregs) in lesional skin ofFlgft/ftmice. Adoptive transfer of WT Tregs dampened the severity of skin lesions inMyD88?/?/Flgft/ftmice. These results suggest that MyD88 signaling in Treg cells by endogenous ligands attenuates skin inflammation in filaggrin deficiency.