001 IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice

Abstract

Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-In skin, various immune cells are activated by invading pathogens or skin damage. Macrophages are vital to innate immunity, and their activation leads to an increased capacity to regulate other cells through the release of cytokines and chemokines that is induced in adaptive immunity 1 . Persistent macrophage activity results in the development of chronic inflammatory skin diseases such as psoriasis and atopic dermatitis (AD) 2 . Abnormal immune conditions of tissues affects the activation and plasticity/polarization of macrophages (i.e. their maturation towards the M1 or M2 state) 3 . The classical pathway is defined as the interferon (IFN)-γ-dependent activation of M1 type macrophages by T helper 1 (Th1)-type responses. The alternative pathway is defined as the M2 type macrophage activation by Th2-type cytokines interleukin (IL)-4, IL-6, IL-10 and IL-13. However, recent studies have shown that the macrophage lineages are diverse and heterogeneous as demonstrated by the presence of unique M1/M2 heterogeneous macrophages in IL-17 immunity.IL-17 family members play an active role in inflammatory diseases and autoimmune diseases 4 . IL-17A is the prototype pro-inflammatory cytokine of the IL-17 family 5 , which is largely produced by activated memory T lymphocytes, and functions to stimulate innate immunity. A well-known IL-17A-related skin disease is psoriasis. The association between IL-17A and psoriasis is well established in humans, mouse and in vitro models 6 . The roles of IL-17A are also implicated in the pathogenesis of AD 7,8 . IL-17A is highly expressed in flaky-tail (Flg ft ) mouse, a murine AD model, that carries mutations in the filaggrin gene 9,10 . Moreover, IL-17A is involved in infectious, inflammatory, neutrophilic, granulomatous, bullous and malignant skin diseases 11 . However, there are few reports regarding the direct effects of IL-17A on the macrophage function in the skin.