Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis. / Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke; Hedegaard, Chris Juul; Søndergaard, Helle B; Krakauer, Martin; Hesse, Dan; Nielsen, Claus H; Sorensen, Per S; Sellebjerg, Finn.

I: P L o S One, Bind 10, Nr. 3, e0118830, 2015, s. 1-20.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Börnsen, L, Christensen, JR, Ratzer, R, Hedegaard, CJ, Søndergaard, HB, Krakauer, M, Hesse, D, Nielsen, CH, Sorensen, PS & Sellebjerg, F 2015, 'Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis', P L o S One, bind 10, nr. 3, e0118830, s. 1-20. https://doi.org/10.1371/journal.pone.0118830

APA

Börnsen, L., Christensen, J. R., Ratzer, R., Hedegaard, C. J., Søndergaard, H. B., Krakauer, M., Hesse, D., Nielsen, C. H., Sorensen, P. S., & Sellebjerg, F. (2015). Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis. P L o S One, 10(3), 1-20. [e0118830]. https://doi.org/10.1371/journal.pone.0118830

Vancouver

Börnsen L, Christensen JR, Ratzer R, Hedegaard CJ, Søndergaard HB, Krakauer M o.a. Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis. P L o S One. 2015;10(3):1-20. e0118830. https://doi.org/10.1371/journal.pone.0118830

Author

Börnsen, Lars ; Christensen, Jeppe Romme ; Ratzer, Rikke ; Hedegaard, Chris Juul ; Søndergaard, Helle B ; Krakauer, Martin ; Hesse, Dan ; Nielsen, Claus H ; Sorensen, Per S ; Sellebjerg, Finn. / Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis. I: P L o S One. 2015 ; Bind 10, Nr. 3. s. 1-20.

Bibtex

@article{0def276092544ecfbba7ce6e4c3ce9c4,
title = "Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis",
abstract = "Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-β-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-β. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-β-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-β are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.",
keywords = "Adult, Biomarkers, CD4-Positive T-Lymphocytes, Cell Proliferation, Female, Gene Expression Regulation, Humans, Interferon Type I, Interferon-beta, Interleukin-10, Intracellular Space, Male, Monocytes, Multiple Sclerosis, Myelin Basic Protein, T-Lymphocyte Subsets",
author = "Lars B{\"o}rnsen and Christensen, {Jeppe Romme} and Rikke Ratzer and Hedegaard, {Chris Juul} and S{\o}ndergaard, {Helle B} and Martin Krakauer and Dan Hesse and Nielsen, {Claus H} and Sorensen, {Per S} and Finn Sellebjerg",
year = "2015",
doi = "10.1371/journal.pone.0118830",
language = "English",
volume = "10",
pages = "1--20",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

AU - Börnsen, Lars

AU - Christensen, Jeppe Romme

AU - Ratzer, Rikke

AU - Hedegaard, Chris Juul

AU - Søndergaard, Helle B

AU - Krakauer, Martin

AU - Hesse, Dan

AU - Nielsen, Claus H

AU - Sorensen, Per S

AU - Sellebjerg, Finn

PY - 2015

Y1 - 2015

N2 - Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-β-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-β. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-β-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-β are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

AB - Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-β-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-β. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-β-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-β are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

KW - Adult

KW - Biomarkers

KW - CD4-Positive T-Lymphocytes

KW - Cell Proliferation

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Interferon Type I

KW - Interferon-beta

KW - Interleukin-10

KW - Intracellular Space

KW - Male

KW - Monocytes

KW - Multiple Sclerosis

KW - Myelin Basic Protein

KW - T-Lymphocyte Subsets

U2 - 10.1371/journal.pone.0118830

DO - 10.1371/journal.pone.0118830

M3 - Journal article

C2 - 25738751

VL - 10

SP - 1

EP - 20

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e0118830

ER -

ID: 162696146