Astrocytes may also contribute to demyelination indirectly via induction of BBB breakdown and expression of chemokines that recruit peripheral immune cells176–180. Human OLs are however resistant to toxic effects of conditioned media from astrocytes preconditioned by immune cell supernatants, whereas immature OL lineage cells are susceptible to impaired differentiation and/or death181. Conversely, immune cells can have protective effects on OLs. Astrocytes indirectly promote OL survival by inducing apoptosis in CD4+ T cells182, and peripheral immune cells in MS produce leukaemia inhibitor factor (LIF) which protects OLs from TNFα-induced death in vitro183. In addition, microglia and astrocytes support OL lineage responses during myelination and remyelination, in part via secretion of growth factors that can act on OL receptors51,138,184,185. Altogether these studies suggest that cell-cell interactions with OLs can have a major influence on OL and myelin pathology in neuroinflammatory diseases such as MS.
