Interleukin-19 alleviates experimental autoimmune encephalomyelitis by attenuating antigen-presenting cell activation

Abstract

Interleukin-19 (IL-19) acts as an anti-inflammatory cytokine in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system, but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the central nervous system. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1{beta}, IL-6, IL-23, TGF-{beta}1, and TNF-. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS.