Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE. Issue 1 (January 2021)

• Record Type: Journal Article
• Authors: Laurent, Cyril; Deblois, Gabrielle; Clénet, Marie-Laure; Carmena Moratalla, Ana; Farzam-kia, Negar; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Larochelle, Catherine; Arbour, Nathalie
• Is Part Of: Neurology. Volume 8:Issue 1(2021)
• Publication Date: 2021-01
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000931
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Objective: We posit that interleukin-15 (IL-15) is a relevant contributor to MS pathobiology as this cytokine is elevated in the CNS and periphery of patients with MS. We aim to investigate (1) the impact of IL-15 on T lymphocytes from patients with MS and (2) the in vivo role of IL-15 using the experimental autoimmune encephalomyelitis (EAE) mouse model. Methods: We compared the impact of IL-15 on T lymphocytes obtained from untreated patients with MS (relapsing-remitting, secondary progressive, and primary progressive) to cells from age/sex-matched healthy controls (HCs) using multiparametric flow cytometry and in vitro assays. We tested the effects of peripheral IL-15 administration after EAE disease onset in C57BL/6 mice. Results: IL-15 triggered STAT5 signaling in an elevated proportion of T cells from patients with MS compared with HCs. This cytokine also enhanced the production of key proinflammatory cytokines (interferon γ, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17, and tumor necrosis factor) by T cells from both MS and controls, but these effects were more robust for the production of IL-17 and GM-CSF in T-cell subsets from patients with MS. At the peak of EAE disease, the proportion of CD4 + and CD8 + T cells expressing CD122 +, the key signaling IL-15 receptor chain, was enriched in the CNS compared with the spleen. Finally, peripheral administration of IL-15 into EAE mice after disease onset significantly aggravated clinical scores and increased the number of inflammatory CNS-infiltrating T cells long term after stopping IL-15 administration. Conclusions: Our results underscore that IL-15 contributes to the amplification of T-cell inflammatory properties after disease onset in both MS and EAE.