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Effect of interferon-β1b on CXCR4-dependent chemotaxis in T cells from multiple sclerosis patients.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2015 Nov; Vol. 182 (2), pp. 162-72. Date of Electronic Publication: 2015 Aug 31. - Publication Year :
- 2015
-
Abstract
- Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease triggered by infiltration of activated T cells into the central nervous system. Interferon (IFN)-β is an established, safe and effective treatment for patients with relapsing-remitting MS (RRMS). The cytokine can inhibit leucocyte infiltration into the central nervous system; however, little is known about the precise molecular mechanisms. Previously, in vitro application of IFN-β1b was shown to reduce CXCL12/CXCR4-mediated monocyte migration. Here, we analysed the effects of IFN-β1b on CXCR4-dependent T cell function. In vitro exposure to IFN-β1b (1000 U/ml) for 20 h reduced CXCR4-dependent chemotaxis of primary human T cells from healthy individuals and patients with RRMS. Investigating the IFN-β1b/CXCR4 signalling pathways, we found no difference in phosphorylation of ZAP70, ERK1/2 and AKT despite an early induction of the negative regulator of G-protein signalling, RGS1 by IFN-β1b. However, CXCR4 surface expression was reduced. Quantitative real time-PCR revealed a similar reduction in CXCR4-mRNA, and the requirement of several hours' exposure to IFN-β1b supports a transcriptional regulation. Interestingly, T cells from MS patients showed a lower CXCR4 expression than T cells from healthy controls, which was not reduced further in patients under IFN-β1b therapy. Furthermore, we observed no change in CXCL12-dependent chemotaxis in RRMS patients. Our results demonstrate clearly that IFN-β1b can impair the functional response to CXCR4 by down-regulating its expression, but also points to the complex in vivo effects of IFN-β1b therapy.<br /> (© 2015 British Society for Immunology.)
- Subjects :
- Adult
Blotting, Western
Cell Movement drug effects
Cells, Cultured
Female
Gene Expression drug effects
Gene Expression immunology
Humans
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting genetics
Multiple Sclerosis, Relapsing-Remitting immunology
Receptors, CXCR4 genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
T-Lymphocytes immunology
T-Lymphocytes metabolism
Time Factors
Young Adult
Chemotaxis drug effects
Interferon beta-1b pharmacology
Receptors, CXCR4 metabolism
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 182
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26212126
- Full Text :
- https://doi.org/10.1111/cei.12689