Monocyte-derived dendritic cells: a potential target for therapy in multiple sclerosis (MS)

Monocytes can differentiate into dendritic cells (DC), cells with a pivotal role in both protective immunity and tolerance. Defects in the maturation or function of DC may be important in the development of autoimmune disease . We sought to establish if there were differences in the cytokine (granulo cyte-macrophage colony-stimulating factor and IL-4)-driven maturation of mo nocytes to DC in patients with MS and whether drugs used to treat MS affect ed this process in vitro. We have demonstrated that there is no defect in t he ability of magnetic activated cell sorting (MACS)-purified monocytes fro m patients with MS to differentiate to DC, but equally they show no tendenc y to acquire a DC phenotype without exogenous cytokines. Interferon-beta1a prevents the acquisition of a full DC phenotype as determined by light and electron microscopy and by flow cytometry. Methylprednisolone not only prev ents the development of monocyte-derived DC but totally redirects monocyte differentiation towards a macrophage phenotype. Evidence is evolving for a role for DC in central nervous system immunity, either within the brain or in cervical lymph nodes. The demonstrated effect of both drugs on monocyte differentiation may represent an important site for immune therapy in MS.