Regulatory T cells promote myelin regeneration in the Central Nervous System

Regeneration of central nervous system (CNS) myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells (OPC). In multiple sclerosis (MS), remyelination can fail despite abundant OPC, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS during MS, yet little is known about T cell functions in remyelination. Here, we report that regulatory T cells (T(reg)) promote oligodendrocyte differentiation and (re)myelination. T(reg)-deficient mice exhibited significantly impaired remyelination and oligodendrocyte differentiation that was rescued by adoptive transfer of T(reg). In brain slice cultures, T(reg) accelerated developmental myelination and remyelination, even in the absence of overt inflammation. T(reg) directly promoted OPC differentiation and myelination in vitro. We identified CCN3 as a novel T(reg)-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of T(reg) in the CNS, distinct from immunomodulation. Although originally named ‘T(reg)’ to reflect immunoregulatory roles, this also captures emerging, regenerative T(reg) functions aptly.