# Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment
## 3 Dendritic Cells  
A lot has been said about the pathogenesis of MS and the role of T-cells in inflammation and demyelination of the CNS. Considering MS as an autoimmune disorder, it could be assumed that initiation of immune reaction is linked with an interplay between the elements of innate and adoptive immunity. As the disease is characterized by a specific immune response toward the CNS myelin antigens, its induction depends on the activation of naive T-cells recognizing processed myelin antigens. Various cell types are able to present antigens for T-lymphocytes; however, only dendritic cells are called the professional antigen-presenting cells--it means that only these cells are capable of priming naive T-cells to differentiation. Since their first description by [PERSON] [30; 31; 32; 33], dendritic cells became considered one of the most important players in the induction of antigen-specific immune responses. Actually, dendritic cells are the aim of newly designed therapeutic strategies in every field where the specific immune response matters (i.e., allergic disorders, cancer therapies, autoimmune disorders) [34]. Because of their biological properties, DCs are thought to be a key players in the initiation of MS, its development, maintenance, and progression. Dendritic cells are heterogeneous group of cells localized in various tissues, where they act as sentinels--filtrating extracellular tissue environment for antigens. In this functional state, dendritic cells possess immature phenotype due to their low ability for antigen presentation, but high endocytic activity and high expression of molecules that facilitates antigen recognition and uptake, for example C-type lectin mannose receptor MR (CD206) or DC-SIGN (CD209). Ingested antigens are processed and presented on the MHC molecules class II (but also class I) on the cell surface. For efficient antigen presentation, antigen uptake must be associated with dendritic cell maturation--which is triggered by danger signals provided with foreign (bacterial or viral) antigens and recognized by DCs via the set of pattern recognition receptors recognizing pathogen-associated molecular patterns [35]. Danger signals may also be provided by tissue destruction and inflammatory cytokines released from other cells. Depending on the recognized signal, located in tissue, immature DCs undergo maturation and their phenotype changes: the expression of antigen uptake receptors as the pinocytic and endocytic activity decreases, whereas the expression of MHC class II and co-stimulatory molecules (CD86, CD83, CD80, CD40) increases. During the maturation, DCs migrate from the tissue via lymph vessels to the draining lymph nodes. Migration to the lymph nodes is regulated by the chemokine milieu. The expression of CCR7 molecules on the surface of maturing DCs regulates their trafficking to the lymph nodes in response to CCL19 and CC21 chemokines [36; 37]. This chemotactic process is also regulated by CXCR4--a receptor for chemokine CXCL12 [38]. In lymph nodes, mature DCs present processed antigens for T-cells, prime their activation, and shape the development of antigen-specific immune response. If the migrated DCs are not activated enough, then the possible result of antigen presentation for T-cells will be the energy of antigen-specific T-cells or induction of Treg cells, resulting in the induction of peripheral tolerance to antigens. Recent findings suggest that the ability of DCs to prime immune tolerance to presented antigen is linked rather with a specific activation state developed after antigen recognition (tolerogenic phenotype) than the lack of maturation. The maturation process occurs, however, into the different phenotype. In MS, the uptake and transport of brain antigens by DCs or another APC cells has been contentious, due to the alleged independence of CNS from the immune system and the presence of BBB, which was believed to block immune cells trafficking into the brain.