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

Publication date: Available online 9 August 2018

Source: Clinical Immunology

Author(s): Sabine Hoff, Michiko K. Oyoshi, Jason L. Hornick, Raif S. Geha, NIH/NIAID funded Atopic Dermatitis Research Network

Abstract

Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient flaky tail (Flg^ft/ft) mice develop spontaneous inflammatory skin lesion that wax and wane. We show that loss of MyD88 promotes the persistence of skin lesions in Flg^ft/ft mice and exaggerates their expression of the Th17-associated cytokines Il7a and Il22. The development and persistence of skin lesions in Flg^ft/ft mice was independent of the microbiota. MyD88-mediated signals are shown to be important for the accumulation of T regulatory cells (Tregs) in lesional skin of Flg^ft/ft mice. Adoptive transfer of WT Tregs dampened the severity of skin lesions in MyD88^−/−/Flg^ft/ft mice. These results suggest that MyD88 signaling in Treg cells by endogenous ligands attenuates skin inflammation in filaggrin deficiency.

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