Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS), leading to neuroinflammation, gliosis, and neuronal loss. The human macrophage galactose-type lectin (MGL or CD301), a member of the C-type lectin receptor (CLR) family, is expressed by myeloid cells such as dendritic cells (DCs) and macrophages. In mice, the macrophage galactose-type lectin 2 (MGL2 or CD301b) receptor is homologous to the human MGL. This study investigates the role of MGL2 in the progression of experimental autoimmune encephalomyelitis (EAE), a murine model replicating MS disease.

DCs play a critical role in regulating myelin-specific T-cell activation in the CNS of MS patients. At the same time, elevated myeloid cells and activated macrophages are associated with demyelination and axonal loss. Given the role of myeloid cells in neuroinflammation, we hypothesize that the CD301b-expressing cells play a role in the EAE disease pathogenesis. 

We used flow cytometry, quantitative real-time polymerase chain reaction (qPCR), RNA-seq, and genetically modified mouse models to investigate the role of CD301b in mouse CNS macrophages and microglia.

We demonstrated that DCs and macrophages in the WT mouse brain express CD301b. When EAE is induced in mouse models, the expression of CD301b in the brain is significantly increased. MGL2-depleted mice showed a later disease onset (p=0.0013), lower maximum clinical score (p=0.0011), and decreased body weight loss compared to their WT littermates. Our data indicates that CD301b-expressing cells play a critical role in EAE pathogenesis.

MGL2-depleted mice developed significantly less severe disease than WT littermates, suggesting CD301b-expressing cells promote EAE progression. Thus, the CD301(b) receptor is a potential therapeutic target, especially considering the role of DCs and macrophages in neuroinflammation. Studies to elucidate CD301’s mechanism of action in MS pathogenesis are underway.