The best basic science paper in multiple sclerosis in 2014: important role for the choroid plexus in the central nervous system entry of leukocytes.

For decades, multiple sclerosis (MS) has been considered to be an autoimmune, inflammatory disease of the central nervous system (CNS), in which CNS self-antigen-specific T cells invade the brain and cause severe tissue destruction. In particular, immune cell presence in the perivascular spaces, the cerebrospinal fluid (CSF) or in the brain parenchyma was almost always considered to be a sign of autoimmune disease or the beginning of such a disease. However, recent data challenge this dogma as these autoreactive T cells do not only induce pathology, but are also required to ensure proper maintenance and repair of the CNS after an inflammatory event, a process defined as resolution. 1 Indeed, under physiological conditions, CNS-patrolling memory T cells are abundantly present in the CSF, where they play an important role (together with the brain-resident innate immune cells like microglia) in the detection of abnormalities (infection, tissue damage) and subsequent resolution in order to restore local tissues to their original/functional state. Consequently, the presence of these CNS-specific T cells is a purposeful process that requires rigorous control, as potential dysregulation may drive CNS pathology. Besides memory T cells, the CSF of MS patients also contains high numbers of pro-inflammatory immune cells 2 and their presence correlates with the number of CNS lesions. 3 MS lesion predilection sites such as periventricular areas, cortex and spinal cord are in close contact with CSF, suggesting that CSF constituents play a vital but yet unknown role in MS pathogenesis. Remarkably, little attention has been given to the choroid plexus (CP), a specialized ventricular structure continuously involved in the production of CSF. However, because of its unique anatomical location, positioned to integrate signals from the brain (via the CSF) and the periphery, this villous structure may actually play an important role in CNS immunity under healthy and pathological conditions. Here, we have selected as the best basic science paper of 2014 the excellent work and breakthrough findings of Michal Schwartz and her group. 1 In her review paper, she summarizes key findings in the last decade that have changed the view on the presence of leuko-cytes in the CNS, indicating that these cells are pivotal players in CNS immune homeostasis as well as in cog-nitive tasks like learning and memory. Moreover, in the highlighted manuscript, the authors describe key in vivo findings that indicate that the CP represents a primary entry site for immune cells upon CNS …