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Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE

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 exp...

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Autores principales: Laurent, Cyril, Deblois, Gabrielle, Clénet, Marie-Laure, Carmena Moratalla, Ana, Farzam-kia, Negar, Girard, Marc, Duquette, Pierre, Prat, Alexandre, Larochelle, Catherine, Arbour, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745728/
https://www.ncbi.nlm.nih.gov/pubmed/33323466
http://dx.doi.org/10.1212/NXI.0000000000000931
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author Laurent, Cyril
Deblois, Gabrielle
Clénet, Marie-Laure
Carmena Moratalla, Ana
Farzam-kia, Negar
Girard, Marc
Duquette, Pierre
Prat, Alexandre
Larochelle, Catherine
Arbour, Nathalie
author_facet Laurent, Cyril
Deblois, Gabrielle
Clénet, Marie-Laure
Carmena Moratalla, Ana
Farzam-kia, Negar
Girard, Marc
Duquette, Pierre
Prat, Alexandre
Larochelle, Catherine
Arbour, Nathalie
author_sort Laurent, Cyril
collection PubMed
description 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.
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spelling pubmed-77457282020-12-23 Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE Laurent, Cyril Deblois, Gabrielle Clénet, Marie-Laure Carmena Moratalla, Ana Farzam-kia, Negar Girard, Marc Duquette, Pierre Prat, Alexandre Larochelle, Catherine Arbour, Nathalie Neurol Neuroimmunol Neuroinflamm Article 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. Lippincott Williams & Wilkins 2020-12-15 /pmc/articles/PMC7745728/ /pubmed/33323466 http://dx.doi.org/10.1212/NXI.0000000000000931 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Laurent, Cyril
Deblois, Gabrielle
Clénet, Marie-Laure
Carmena Moratalla, Ana
Farzam-kia, Negar
Girard, Marc
Duquette, Pierre
Prat, Alexandre
Larochelle, Catherine
Arbour, Nathalie
Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title_full Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title_fullStr Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title_full_unstemmed Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title_short Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
title_sort interleukin-15 enhances proinflammatory t-cell responses in patients with ms and eae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745728/
https://www.ncbi.nlm.nih.gov/pubmed/33323466
http://dx.doi.org/10.1212/NXI.0000000000000931
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