UCSF

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.