Cited by 557Multiple Sclerosis Research StudiesPsoriasis: Treatment and PathogenesisT-cell and B-cell Immunology

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Preferential recruitment of interferon‐γ–expressing T H 17 cells in multiple sclerosis

Kebir, Hania, Ifergan, Igal, Alvarez, Jorge Ivan, Bernard, Monique, Poirier, Josée, Arbour, Nathalie, Duquette, Pierre, Prat, Alexandre·2009·Annals of Neurology

DOI 10.1002/ana.21748

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Abstract

Objective: There is substantial evidence supporting the role of interferon (IFN)‐γ–producing T helper (T H ) 1 and interleukin (IL)‐17–expressing T H 17 lymphocytes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). However, to date little is known about the potential cooperative interplay between these 2 cytokines. In the current study, we sought to evaluate the frequency of IFN‐γ–expressing T H 17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS). Methods: Human T H 17 lymphocytes were expanded in vitro from the blood of healthy controls and relapsing MS patients using IL‐23. Immune cell migration to the CNS was assessed in vitro with primary cultures of human blood–brain barrier (BBB)‐derived endothelial cells, and in vivo in EAE mice. Results: We demonstrate that in response to IL‐23, human memory lymphocytes expand into a T H 17 phenotype, with a subpopulation of cells simultaneously expressing IFN‐γ and IL‐17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN‐γ–producing T H 17 cells and identify numerous T lymphocytes coexpressing IL‐17 and IFN‐γ in brain tissue of MS patients. We also find lymphocytes expressing both the T H 1‐ and the T H 17‐associated transcription factors RORγt and T‐bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN‐γ + T H 17 lymphocytes preferentially cross the human BBB and accumulate in the CNS of mice during the effector phase of EAE. Interpretation: Our data underscore the involvement of IFN‐γ + T H 17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events. Ann Neurol 2009;66:390–402

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Authors: Kebir, H., Ifergan, I., Alvarez, J. I., Bernard, M., Poirier, J., Arbour, N., Duquette, P., & Prat, A.
Affiliations: Hôpital Notre-Dame (CA)
Corresponding author: Prat, Alexandre
ORCID: Ifergan, Igal
Alvarez, Jorge Ivan
Poirier, Josée
Arbour, Nathalie
Duquette, Pierre
Prat, Alexandre
Venue: Annals of Neurology
Publisher: Wiley
Published: 2009-09
Volume: 66
Issue: 3
Pages: 390-402
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.21748
OpenAlex: W2127568644
Cited by: 551
References: 39
Citations by year: 2026: 13 · 2025: 17 · 2024: 20 · 2023: 36 · 2022: 34 · 2021: 38 · 2020: 27 · 2019: 35 · 2018: 34 · 2017: 40 · 2016: 37 · 2015: 47 · 2014: 42 · 2013: 36 · 2012: 29
FWCI: 22.07
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 35 d)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, Th17 cells, interferon-gamma, IL-17, IL-23, blood-brain barrier, T-bet, memory T cells, relapsing multiple sclerosis
MeSH terms: Adult, Animals, Blood-Brain Barrier, Brain, Cell Migration Inhibition, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Interferon-gamma, Mice, Inbred C57BL, Middle Aged, Multiple Sclerosis, T-Lymphocytes, Th1 Cells, Th2 Cells, Interleukin-17, Multiple Sclerosis, Relapsing-Remitting, Mice, Interleukin-23, Cell Migration Assays, In Vitro Techniques

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Preferential recruitment of interferon‐γ–expressing T H 17 cells in multiple sclerosis

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