Type I IFN Derived from Ly6C^hi Monocytes Suppresses Type 2 Inflammation in a Murine Model of Atopic Dermatitis

The roles of innate immune cells, including eosinophils, basophils, and group 2 innate lymphoid cells, in atopic dermatitis (AD) have been well-documented, whereas that of monocytes, another component of the innate immunity, remains rather poorly understood, thus necessitating the topic of this study. In addition, cytokines and cellular pathways needed for the resolution of type 2 inflammation in AD need further investigation. Using a murine AD model, we report here that (i) Ly6C^hi monocytes were rapidly recruited to the AD lesion in a CCR2-dependent manner, blockade of which exacerbated AD; (ii) type I IFN production is profoundly involved in this suppression because the blockade of it by genetic depletion or antibody neutralization exacerbated AD; and (iii) Ly6C^hi monocytes operate through the production of type I IFN because Ly6C^hi monocytes from Irf7-null mice, which lack type I IFN production, failed to rescue Ccr2^-/- mice from severe AD upon adoptive transfer. In addition, in vitro studies demonstrated type I IFN suppressed basophil expansion from bone marrow progenitor cells and survival of mature basophils. Collectively, our work suggests that Ly6C^hi monocytes are the first and dominant inflammatory cells reaching AD lesions that negatively regulate type 2 inflammation through the production of type I IFN.