Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis.
Interferon-beta (IFNbeta) 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 IFNbeta treatment suppresses Th17 cells' differentiation, mediated by its effects on dendritic cells (DCs), B-cells and T-cells. IFNbeta 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-1b and IL-23 is mediated via induction of suppressor of cytokine signaling (SOCS)3 expression. In naïve CD45RA+ T-cells, IFNbeta directly suppresses Th17 cells' differentiation, as evidenced by the suppression of this cell subset's 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 IFNbeta-mediated induction of IL-10 in T-cells and B-cells represents an important additional immunoregulatory mechanism. Described IFNbeta's mechanisms of action selectively target Th17 cell-mediated autoimmune responses in patients with RR MS.
Ramgolam
Vinod S
VS
Department of Neurology, University of North Carolina at Chapel Hill, USA.
Markovic-Plese
Silva
S
D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
D016899:Interferon-beta