Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS.

Adult Cross-Sectional Studies Female Humans Interleukin-1beta / immunology Lymphocyte Activation / drug effects Male Middle Aged Monocytes / drug effects Multiple Sclerosis, Relapsing-Remitting / drug therapy Quinolones / therapeutic use Signal Transduction / drug effects Th17 Cells / immunology

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
01 2021
Historique:
received: 11 05 2020
accepted: 23 09 2020
entrez: 18 11 2020
pubmed: 19 11 2020
medline: 13 10 2021
Statut: epublish

Résumé

To assess the impact of laquinimod treatment on monocytes and to investigate the underlying immunomodulatory mechanisms in MS. In this cross-sectional study, we performed in vivo and in vitro analyses of cluster of differentiation (CD14 Laquinimod did not alter the frequency or viability of circulating monocytes, but led to an upregulation of CD86 expression. LPS-stimulated monocytes of laquinimod-treated patients with MS secreted less IL-1β following a downregulation of IL-1β gene expression. Phosphorylation levels of the NF-κB p65 subunit were reduced after laquinimod treatment, indicating a laquinimod-associated inhibition of the NF-κB pathway. T cells primed with laquinimod-treated monocytes differentiated significantly less into IL-17A-producing T helper (Th)-17 cells. Our findings suggest that inhibited NF-κB signaling and downregulation of IL-1β expression in monocytes contributes to the immunomodulatory effects of laquinimod and that the impairment of Th17 polarization might mediate its disease-modifying activity in MS.

Identifiants

DOI: 10.1212/NXI.0000000000000908 PMID: 33203651 PMC: PMC7676421
pubmed: 33203651
pii: 8/1/e908
doi: 10.1212/NXI.0000000000000908
pmc: PMC7676421
pii:
doi:

Substances chimiques

IL1B protein, human 0
Interleukin-1beta 0
Quinolones 0
laquinimod 908SY76S4G

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Sinah Engel (S)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0002-9051-9062

Valérie Jolivel (V)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Stefan H-P Kraus (SH)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Morad Zayoud (M)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Karolina Rosenfeld (K)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Hayrettin Tumani (H)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Roberto Furlan (R)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Florian C Kurschus (FC)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.

Ari Waisman (A)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0003-4304-8234

Felix Luessi (F)

From the Department of Neurology (S.E., V.J., S.H.-P.K., K.R., F.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University of Mainz, Germany; Biopathology of Myelin (V.J.), Neuroprotection and Therapeutic Strategy, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, France; Institute for Molecular Medicine (M.Z., F.C.K., A.W.), University Medical Centre of the Johannes Gutenberg University of Mainz, Germany; Sheba Cancer Research Center (M.Z.), Chaim Sheba Academic Medical Center, Ramat Gan, Israel; Department of Neurology (H.T.), University of Ulm, Germany and Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany; Clinical Neuroimmunology Unit (R.F.), San Raffaele Scientific Institute, Milan, Italy; and Department of Dermatology (F.C.K.), Heidelberg University Hospital, Heidelberg, Germany. luessi@uni-mainz.de.
ORCID: 0000-0003-4334-4199

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Monokines › Interleukine-1 › Interleukine-1 bêta › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Monocytes › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Sclérose en plaques récurrente-rémittente › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Quinolinone › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Laquinimod dampens IL-1β signaling and...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T auxiliaires › Cellules Th17 › Laquinimod dampens IL-1β signaling and...