Regulatory Cells in Multiple Sclerosis: From Blood to Brain

Multiple sclerosis (MS) is a chronic, autoimmune, and neurodegenerative disease of the central nervous system (CNS) that affects myelin. The etiology of MS is unclear, although a variety of environmental and genetic factors are thought to increase the risk of developing the disease. Historically, T cells were considered to be the orchestrators of MS pathogenesis, but evidence has since accumulated implicating B lymphocytes and innate immune cells in the inflammation, demyelination, and axonal damage associated with MS disease progression. However, more recently the importance of the protective role of immunoregulatory cells in MS has become increasingly evident, such as that of myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) and B (Breg) cells, or CD56^bright natural killer cells. In this review, we will focus on how peripheral regulatory cells implicated in innate and adaptive immune responses are involved in the physiopathology of MS. Moreover, we will discuss how these cells are thought to act and contribute to MS histopathology, also addressing their promising role as promoters of successful remyelination within the CNS. Finally, we will analyze how understanding these protective mechanisms may be crucial in the search for potential therapies for MS.