# Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment
## 4 MS-Approved Drugs Targeting Immunocompetent Cells
### Dendritic Cells in MS Therapy  
As a key player in the initiation and maintenance of antigen-specific immune response, dendritic cells are considered not only as a target for drug-based treatment. The use of specific tolerogenic dendritic cells is also considered a therapeutic option. The idea of using tolerance-inducing dendritic cells depends on the use of antigen-loaded DCs primed to tolerogenic phenotype, which are able to polarize the immune response against presented antigens towards the induction of immune tolerance, which results in the expansion of antigen-specific regulatory T-cells. Phenotype of tolerance-inducing DCs is traditionally characterized as semi-mature with weak expression of MHC class II molecules and co-stimulatory receptors (CD86, CD83, CD80, CD40), high level of surface inhibitory molecules (PDL1/2, ILT3, ILT4), and specific secretory activity with evident IL-10 or TGF-\(\beta\) production and weak release of proinflammatory cytokines [122]. Induction of tolerance to antigens depends mainly on the ability of DCs to promote differentiation of naive T-cells to Treg during antigen presentation in lymph nodes. Moreover, tolerance-inducing DCs were also reported to be able to inhibit the proliferation of T-cells, induce T-cells hyporesponsiveness, and T-cells anergy [123; 124; 125]. The level of conventional DCs in circulating blood is quiet low; thus, in numerous studies, DCs are derived from blood monocytes. Standard protocol utilizes moDCs differentiation from monocytes in the presence of IL-4 and GM-CSF to immature DCs [126; 127]. Tolerogenic phenotypes may be obtained in numerous ways; the most popular utilizes vitamin D3 or IL-10; however, the use of corticosteroids, rapamycin, or specific NF-\(\kappa\)B inhibitors were also described as possible strategies [128]. Up to date, the most interesting and well-studied are tolerogenic DCs induced by vitamin D3 or glycocortycosteroid dexamethasone. In vitro and animal studies with vitD3-tolDC confirmed their ability to induce hyporesponsiveness of T-cells toward presented antigens, as well as the stability of promoted tolerogenic phenotype, which was not abol \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Drug** & **Molecular** & **Delivery Route** & **Molecular Target** & **Action** & **Remarks** & **References** \\ \hline \hline \multirow{8}{*}{Drug} & \multirow{8}{*}{Molecular Characteristic} & \multirow{8}{*}{Delivery Route} & Anti- & & \\  & & & inflammatory & & \\  & & & immune response & & \\  & & & Alteration of & & \\  & & & & Th-cell & & \\  & & & & & & \\  & & & & Induction of & & \\  & & & & regulatory T-cells & & \\  & & & & Activation of & & \\  & & & & Nrf-dependent & & \\  & & & & & metasurfaces in CD8+ & \\  & & & NRF2-dependent & & T-cells, B-cells, & \\  & & & pathways, & and myeloid & & \\  & & & & hydroxyl & dendritic cells & & \\  & & & & receptor 2 & & \\  & & & & (HCAR2) & & \\  & & & & & neutrophil & \\  & & & & infiltration in & & \\  & & & & CNS & & \\  & & & & Inhibition of & & \\  & & & & microglia & & \\  & & & & activation & & \\  & & & & Reduced & & \\  & & & & & activation state of & \\  & & & & dendritic cells, & & \\  & & & & M2 monocytes, & & \\  & & & & T-cells, NK-cells & & \\  & & & Activation of & & \\  & & & & & & \\  & & & & & \\  & & & & & & \\  & & & & & & \\ \end{tabular}
\end{table} 
Table 1: _Cont._ished by cryopreservation [129; 130]. Animal studies conducted using an EAE model revealed the potential of myelin antigen-loaded tolDC administration to suppress immune response and enhance the proliferation of regulatory B-cells and T-cells. Recently, [PERSON] et al. identified CD115 (CSF1R) as a biomarker for tolerogenic properties of DCs, which is also involved in the vitamin D-mediated induction of tolerogenic phenotypes. What is more, authors reported CSF1R-CSF1 signaling to be important for metabolic reprogramming of vitamin D-modulated DCs, related with elevated glucose uptake and lactate production [131].