Interleukin-27 is locally produced and triggers responses in the inflamed human CNS

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Nathalie Arbour

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

The mechanisms whereby CNS cells locally modulate immune responses are not fully elucidated. Our goal is to determine whether interleukin-27 (IL-27), a cytokine with both pro- and anti-inflammatory properties, contributes to the pathogenesis of multiple sclerosis (MS), the prototypic neuroinflammatory disease. IL-27 is composed of two subunits: EBI3 and p28 whereas its receptor (IL-27R) consists of two chains: TCCR and gp130. We observed that IL-27 is up-regulated in MS brains compared to controls and that astrocytes (GFAP+) and microglia/macrophages (Iba1+) are important sources of this cytokine. We demonstrated that pro-inflammatory cytokines (e.g. TNF) up-regulate IL-27 production by human astrocytes. Human pro-inflammatory macrophages and microglia (M1 cells) also produce high levels of IL-27, whereas anti-inflammatory (M2 cells) do not. Moreover, we detected that most CNS infiltrating CD8 T lymphocytes express the IL-27R, supporting the notion that these infiltrating immune cells are susceptible to the local IL-27-mediated effects. We have previously shown that IL-27 promotes the activation of human CD8 T-lymphocytes into Tc1 cells, thus CNS sources of IL-27 could locally increase cytotoxic function of these infiltrating T cells. Finally, IL-27 triggers signaling into human astrocytes suggesting that these CNS cells are also receptive to this cytokine. Overall, our data demonstrate that IL-27 and its receptor are elevated in the CNS of MS patients and that several cells (T lymphocytes, astrocytes) present in such inflamed CNS are susceptible to this cytokine. We are currently investigating whether elevated IL-27 levels within the CNS are beneficial or detrimental in the context of MS..