Effect of interferon‐β1b on CXCR4‐dependent chemotaxis in T cells from multiple sclerosis patients

Summary 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.