Allergic Skin Inflammation Drives IL-4-Dependent Differentiation of Dermal CD11b-low Dendritic Cells.

Abstract

IL-13 produced by type 2 innate lymphoid cells is crucial for the steady-state differentiation of dermal CD11b-low type 2 dendritic cells (DC2s), a murine KLF4-dependent DC2 population that is found only in the skin and drives enhanced T helper 2 differentiation. In this study, we examined how CD11b-low DC2s respond to skin inflammation, particularly in the absence of IL-13. We employed a model of MC903-induced atopic dermatitis in which CD11b-low DC2s migrate from skin to the draining lymph node in a TSLP receptor-dependent manner, temporarily depleting the skin CD11b-low population. In C57BL/6J mice, DC2s replenished the empty niche gradually over several days and required IL-4RA-dependent signaling for their differentiation into CD11b-low DC2s. In IL-13 knockout mice treated with MC903, IL-4 produced by basophils and CD4+ T cells could compensate for the absence of IL-13 to drive differentiation of skin CD11b-low DC2s. We confirmed this latter finding by showing that IL-4 treatment was sufficient to induce CD11b-low differentiation both in DC cultures and in IL-13 knockout mice. Our findings suggest that in the absence of IL-13, IL-4 produced during type 2 skin inflammation can induce CD11b-low DC2 differentiation, providing insight into how inflammation can drive an environment that supports further allergic sensitization.