CNS-localized myeloid cells capture living invading T cells during neuroinflammation

Area of Science:

• Neuroimmunology
• Cellular Biology
• Pathogenesis of Multiple Sclerosis

Background:

• Multiple sclerosis (MS) pathogenesis involves complex interactions within the central nervous system (CNS).
• The role of myeloid cells in CNS immune responses during MS and its animal model, experimental autoimmune encephalomyelitis (EAE), requires further elucidation.

Purpose of the Study:

• To investigate the direct interactions between myeloid cells and pathogenic T cells in the CNS.
• To explore the mechanisms underlying myeloid cell engulfment of T cells and its therapeutic potential in EAE.

Main Methods:

• Intravital microscopy was employed to observe cellular interactions in vivo in EAE models.
• Organotypic hippocampal slice cultures were used for ex vivo analysis of myeloid-T cell interactions.
• Flow cytometry and molecular assays were utilized to identify key molecular mediators.

Main Results:

• Myeloid cells were observed to actively engulf live Th17 lymphocytes in the CNS.
• This engulfment process is mediated by an activation-dependent lectin on myeloid cells and N-acetyl-D-glucosamine (GlcNAc) on T cells.
• Enhancing GlcNAc exposure on T cells ameliorated clinical symptoms of EAE, indicating therapeutic efficacy.

Conclusions:

• Myeloid cells possess a direct mechanism to eliminate invading pathogenic T cells in the CNS.
• T cell engulfment by myeloid cells represents a novel first-defense pathway against CNS invasion.
• Targeting T cell-myeloid cell interactions, specifically GlcNAc-mediated engulfment, offers a promising therapeutic strategy for MS and EAE.