The impact of IL-27 on human T cells is altered in multiple sclerosis patients

Abstract

Abstract IL-27 exhibits pro- and anti-inflammatory properties. This cytokine dampens the severity of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Whether IL-27 plays a role in pathobiology of the human disease is still unresolved. We recently showed that both IL-27 and IL-27Receptor (IL-27R composed of IL-27Rα and gp130 chains) are elevated in MS brains compared to controls. We reported expression of IL-27R by brain-infiltrating CD4 and CD8 T cells in MS tissues. To determine whether IL-27 contributes to altered immune responses in MS, we investigated the impact of this cytokine on peripheral blood T cells obtained from untreated MS patients and age/sex-matched healthy donors. Surface IL-27R is present on lower proportions of effector memory (CCR7−) CD4 and CD8 T cells compared to naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RO+) counterparts in all donors. However, reduced proportions of all CD4 T cell subsets but enhanced percentages of CD8 T cell subsets express IL-27R in MS patients compared to controls. IL-27 triggers rapid phosphorylation of STAT1 and STAT3 in all T cell subsets. The percentage and intensity of pSTAT1 detection in all T cell subsets were similar in both donor groups. In contrast, increased proportions of all CD4 and CD8 T cell subsets express pSTAT3 in response to IL-27 compared to cells from controls. Finally, elevated amounts of both IL-27 and its recently identified natural antagonist (soluble) IL-27Rα are present in serum from MS patients compared to controls. Thus, our results reveal that IL-27 has an altered impact on T cells from MS patients which could contribute to aberrant immune responses associated with this inflammatory/autoimmune disease of the central nervous system.