Regulatory T cells promote myelin regeneration in the central nervous system

Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (T_reg) promote oligodendrocyte differentiation and (re)myelination. T_reg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which 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 oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a 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 the cells were originally named 'T_reg' to reflect immunoregulatory roles, this also captures emerging, regenerative T_reg functions.