# Glatiramer Acetate Modifies the Immune Profiles of Monocyte-Derived Dendritic Cells In Vitro Without Affecting Their Generation

## TL;DR

Glatiramer acetate does not prevent monocyte-derived dendritic cell formation but alters their immune-related functions in a way that could be beneficial for treating multiple sclerosis.

## Contribution

The study reveals that GA modifies immune profiles of dendritic cells without affecting their generation, offering new insights into its therapeutic mechanism.

## Key findings

- GA treatment does not hinder monocyte differentiation into dendritic cells or macrophages.
- GA increases antigen recognition and co-stimulation molecule expression in dendritic cells.
- GA downregulates CD1a and upregulates CD68 in monocyte subsets.

## Abstract

Glatiramer acetate (GA) is the first-line therapy for relapsing-remitting multiple sclerosis (MS) and is increasingly demonstrating promising therapeutic benefits in a range of other conditions. Despite its extensive use, the precise pharmacological mechanism of GA remains unclear. In addition to T and B cells, dendritic cells (DCs) and monocytes play significant roles in the neuroinflammation associated with MS, positioning them as potential initial targets for GA. Here, we investigated GA’s influence on the differentiation of human monocytes from healthy donors into monocyte-derived dendritic cells (moDCs) and assessed their activation status. Our results indicate that GA treatment does not hinder the differentiation of monocytes into moDCs or macrophages. Notably, we observed a significant increase in the expression of molecules required for antigen recognition, presentation, and co-stimulation in GA-treated moDCs. Conversely, there was a significant downregulation of CD1a, which is crucial for activating auto-aggressive T cells that respond to the lipid components of myelin. Furthermore, GA treatment resulted in an increased expression of CD68 on both CD14+CD16+ and CD14+CD16− monocyte subsets. These in vitro findings suggest that GA treatment does not impede the generation of moDCs under inflammatory conditions; however, it may modify their functional characteristics in potentially beneficial ways. This provides a basis for future clinical studies in MS patients to elucidate its precise mode of action.