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Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation

Horiuchi, H;Parajuli, B;Komiya, H;Ogawa, Y;Jin, S;Takahashi, K;Azuma, YT;Tanaka, F;Suzumura, A;Takeuchi, H;

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory
response of macrophages and microglia in autocrine/paracrine manners in various
inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease
in the central nervous system (CNS), 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 CNS. In
addition, IL-19-deficient splenic macrophages expressed elevated levels of major
histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell
differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α.
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.