Inflammation-induced epigenetic memory restores oligodendrocyte progenitor cell regenerative capacity in the aged central nervous system

Abstract

Although remyelination, a central nervous system (CNS) regenerative process mediated by oligodendrocyte progenitor cells (OPCs), takes place in an inflammatory environment the long-term impact of inflammation on OPC remyelination capacity remains unclear. Here, we studied the short- and long-term impact of systemic inflammation on adult OPCs to assess whether transient inflammation triggers enduring chromatin remodelling indicative of inflammatory memory in OPCs. We observed long-lasting epigenetic modifications in response to both lipopolyssaccharide (LPS) and polyinosinic:polycytidylic acid (Poly(I:C)), but only LPS induced a tolerance-like memory. LPS-mediated tolerance-like memory enhanced OPC differentiation after demyelination in aged mice, reducing axonal damage. Our findings reveal OPC epigenetic memory of inflammation as a mechanism by which adult OPCs adapt to inflammatory challenges, which could be harnessed to reduce neuroinflammation and enhance remyelination efficiency in ageing and neurodegenerative diseases.