Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Type I Interferon derived from Ly6Chi monocytes suppresses type 2 inflammation in murine model of atopic dermatitis.

Abstract

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 and thus the topic of this study. Additionally, 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 1) Ly6Chi monocytes were rapidly recruited to the AD lesion by a CCR2-dependent manner, blockade of which exacerbated AD. 2) Type I IFN production is profoundly involved in this suppression as the blockade of it by genetic depletion or antibody neutralization exacerbated AD. 3) Ly6Chi monocytes operates through the production of type I IFN because Ly6Chi monocytes from Irf7-null mice which lack type I IFN production, failed to rescue Ccr2-/- mice from severe AD upon adoptive transfer. Additionally, 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 Ly6Chi monocytes are the first and dominant inflammatory cells reaching AD lesion that negatively regulate type 2 inflammation, through the production of type I IFN.