Abstract
Interferon-beta (IFNβ) has been used over the past 15 years as a first-line therapy for relapsing remitting multiple sclerosis (RR MS), however its mechanisms of action are still not completely elucidated. Recently discovered Th17 cells have been hypothesized to play a crucial role in the development of autoimmune diseases, including MS. Studies from our laboratory and others have demonstrated that IFNβ treatment suppresses Th17 cells differentiation, mediated by its effects on dendritic cells (DCs), B-cells and T-cells. IFNβ induces the production of the Th17-suppressive cytokines interleukin (IL)-27 and IL-12 in DCs and B-cells through the phosphorylation of signal transducers and activators of the transcription protein (STAT)1. Its inhibition of the Th17-promoting cytokines IL-1β and IL-23 is mediated via induction of suppressor of cytokine signaling (SOCS)3 expression. In naive CD45RA+ T-cells, IFNβ directly suppresses Th17 cells differentiation, as evidenced by the suppression of this cell subsets specific transcription factor retinoic acid-related orphan receptor (ROR)c, cytokine IL-17A and the surface markers chemokine receptor (CCR)6 and IL-23R. The IFNβ-mediated induction of IL-10 in T-cells and B-cells represents an important additional immunoregulatory mechanism. Described IFNβs mechanisms of action selectively target Th17 cell-mediated autoimmune responses in patients with RR MS.
Keywords: Interferon-beta, multiple sclerosis, Th17 cells, dendritic cells, B-cells, innate immune response
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: Interferon-beta Inhibits Th17 Cell Differentiation in Patients with Multiple Sclerosis
Volume: 10 Issue: 2
Author(s): Vinod S. Ramgolam and Silva Markovic-Plese
Affiliation:
Keywords: Interferon-beta, multiple sclerosis, Th17 cells, dendritic cells, B-cells, innate immune response
Abstract: Interferon-beta (IFNβ) has been used over the past 15 years as a first-line therapy for relapsing remitting multiple sclerosis (RR MS), however its mechanisms of action are still not completely elucidated. Recently discovered Th17 cells have been hypothesized to play a crucial role in the development of autoimmune diseases, including MS. Studies from our laboratory and others have demonstrated that IFNβ treatment suppresses Th17 cells differentiation, mediated by its effects on dendritic cells (DCs), B-cells and T-cells. IFNβ induces the production of the Th17-suppressive cytokines interleukin (IL)-27 and IL-12 in DCs and B-cells through the phosphorylation of signal transducers and activators of the transcription protein (STAT)1. Its inhibition of the Th17-promoting cytokines IL-1β and IL-23 is mediated via induction of suppressor of cytokine signaling (SOCS)3 expression. In naive CD45RA+ T-cells, IFNβ directly suppresses Th17 cells differentiation, as evidenced by the suppression of this cell subsets specific transcription factor retinoic acid-related orphan receptor (ROR)c, cytokine IL-17A and the surface markers chemokine receptor (CCR)6 and IL-23R. The IFNβ-mediated induction of IL-10 in T-cells and B-cells represents an important additional immunoregulatory mechanism. Described IFNβs mechanisms of action selectively target Th17 cell-mediated autoimmune responses in patients with RR MS.
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Cite this article as:
S. Ramgolam Vinod and Markovic-Plese Silva, Interferon-beta Inhibits Th17 Cell Differentiation in Patients with Multiple Sclerosis, Endocrine, Metabolic & Immune Disorders - Drug Targets 2010; 10 (2) . https://dx.doi.org/10.2174/187153010791213029
DOI https://dx.doi.org/10.2174/187153010791213029 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
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