# Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment
## 3 Dendritic Cells
Recent findings have finally shown that dendritic cells may also be present in the central nervous system not only during inflammation, but also at steady-state conditions. It is discussible whether DCs may home the brain parenchyma; however, it is already confirmed that these cells are present in choroid plexus, perivascular spaces of BBB, meninges, and in cerebrospinal fluid. Their presence seems to be the effect of migration of bone marrow precursors from blood [39]. It was also found that microglia cells--brain-specific macrophages--may differentiate into immature dendritic cells after GM-CSF stimulation [40]; however, the comparative microarray analysis of gene expression profile suggests the close resemblance of the brain DCs to the dendritic cells of spleen, but not to the microglia [41]. Localization of DCs in close proximity to neurons gives a chance for myelin antigens uptake and initiation disease-specific immune response. The myelin antigens uptake and the source of danger signals are still open and unsolved questions. It seems rather unbelievable that myelin antigens alone may provide the efficient signal for DCs' activation and maturation; however, coexisting viral infections as well as local physical injuries may strengthen the danger signal. Another aspect of specific immune response is the place of naive T-cells priming by antigen-loaded mature DCs. On periphery, antigen-processing DCs migrate to the draining lymph nodes via lymphatic vessels. However, there is no typical lymphatic drainage of the brain and the exact path for dendritic cells' migration is not yet fully identified. However, observations on animal models describe the presence of labeled OVA antigens in cervical lymph nodes after its intracerebral injection into the brain [42]. Accumulation of myelin-loaded CD11c-positive dendritic cells in cranial lymph nodes was also reported [43]. Studies on dendritic cells loaded with antigens and injected into the cerebellum or CSF also reported their movement to the cervical lymph nodes and localized their antigen presentation [44; 45]. The exact route for cells migration from brain to draining lymph nodes is not fully identified. Recent studies describe the role of meningeal lymphatic vessels as a route for antigen-loaded cells from the brain to the cranial lymph nodes [46; 47; 48]. Another route for antigen-presenting cells from the brain to the peripheral lymph nodes was reported by [PERSON] et al., where injection of monocyte-derived DCs into the striatum resulted in their perivascular accumulation and migration across the endothelium into the vessel lumen [49]. The third possible route for CD11c-positive DCs was reported by [PERSON] et al. and utilizes olfactory bulb and rostral migratory stream [50]. The separate issue is the possible role of microglia cells as potential professional APCs and their possible role in initiation of antigen-specific immune response in MS. Microgliaare cells that are located in the brain parenchyma in the close proximity to myelin. The recent findings of [PERSON] et al. suggest the possible ability of microglia cells to migrate from the brain parenchyma to cervical lymph nodes for antigen presentation [51]. Microglia represents a subset of CNS resident cells with macrophage-like morphology, derived from early post-embryonic precursors. In resting state, ramified microglia continually surveys the microenvironment for threats. The activated amoeboid microglia have round or oval shape, process antigens, and clear them from the vicinity. Microglia may be divided into two subgroups: M1, which promote inflammation and oligodendrocyte damage, and M2, which regulate immune function, clear cellular debris, and promote repair in inflammatory diseases of the CNS [52,53]. However, now, it is assumed that microglia may differentiate into various subtypes with diverse functions, which is affected by a variety of environmental stimuli [54, 55, 56, 57, 58].