Epicutaneous antigen challenge of orally sensitized mice elicits allergic dermatitis by redirecting α4β7 gut homing T cells to the skin (79.7)

Abstract

Abstract Patients with atopic dermatitis (AD) can develop skin flares after ingestion of food allergens or cutaneous contact with these antigens. We examined the mechanism by which cutaneous exposure to allergens in orally sensitized individuals may elicit allergic skin inflammation. Wild-type (WT) or CC chemokine receptor (CCR)4-/- mice were fed intragastrically once a week for eight weeks 5 mg ovalbumin (OVA) and 10 μg cholera toxin (CT) in 200 μL saline or with CT alone in saline. Mice were then epicutaneously (EC) challenged with 100 μg OVA or saline. Mice were sacrificed a week later and analyzed for allergic skin inflammation. For adoptive transfer, CD4+α4β7+ T cells were purified from mesenteric lymph node (MLN) of orally sensitized WT or CCR4-/- mice and administered to WT recipients followed by EC challenge with OVA. Mice orally immunized with OVA then EC challenged with OVA developed allergic skin inflammation characterized by dermal infiltration with eosinophils and CD4+ T cells and upregulation of Th2 cytokines mRNA expression. In contrast to WT mice, orally immunized CCR4-/- mice failed to develop allergic skin inflammation in response to EC challenge. Purified CD4+α4β7+ T cells from MLN of orally immunized WT mice, but not CCR4-/- mice, transferred allergic skin inflammation to WT recipients. These results suggest that CD4+α4β7+ T cells educated in the gut can be reprogrammed in vivo to home to the skin in a CCR4 dependent manner and cause allergic skin inflammation in response to cutaneous antigen exposure. Funded by The Atopic Dermatitis and Vaccinia Network NIH/NIAID contract N01 AI40030