Neural precursor cells as a novel target for interferon-beta

The immunomodulating agent interferon-β (IFNβ) is administered therapeutically in several autoimmune diseases and endogenously released by immune cells during diverse infections. As in recent years a variety of pro- and anti-inflammatory substances were shown to influence significantly neural precursor cells that are implicated in a variety of regenerative mechanisms but also in tumor growth, we studied a possible effect of IFNβ on neural precursor cells derived from murine embryonic day 14 neurospheres. First, we demonstrated that interferon type-I receptors are expressed on neural precursor cells and that these cells respond to IFNβ treatment by up-regulating IFNβ inducible genes including Myxovirus 1 and viperin. Furthermore, we could show for the first time that IFNβ treatment significantly inhibited the proliferation of neural precursor cells possibly through induction of p21, a cyclin-dependent kinase inhibitor. IFNβ did not exert cytotoxic or neuroprotective effects and we could not see effects on the differentiation of neural precursor cells into total amounts of neurons, astrocytes or oligodendrocytes. However, we found that IFNβ markedly diminished neurite outgrowth and neuronal maturation of neural precursor-derived neurons.