Glycome remodeling programs pathogenic γδ T17 cell responses in autoimmunity.

Glycome remodeling of γδ T cells, specifically loss of branched N-glycans, programs pathogenic IL-17A responses linked to severe psoriasis.

• Why it matters: Understanding how glycosylation influences γδ T cell activation and function is crucial because these cells play key roles in host defense, tissue homeostasis, and autoimmune diseases, yet their glycome landscape remains largely unexplored.
• What they did: Single-cell RNA sequencing revealed that type 3 γδ T17 cells depend on MGAT1-MGAT5 mediated branched N-glycosylation, and absence of these glycans shifts their phenotype toward pro-inflammatory and innate-like properties, with deficiency observed in patients with autoimmune diseases.
• The result: Glycan supplementation reprograms γδ T cells toward a less pathogenic state, suggesting N-glycans as a novel immune checkpoint that could be targeted to modulate pathogenic γδ T17 cell responses in autoimmunity.