Antigen presentation by CD40(+)MHC-II(+) astrocytes promotes CNS autoimmunity.

CD40(+)MHC-II(+) astrocytes actively promote CNS autoimmunity by enhancing pathogenic T helper 17 responses, with 40% of astrocytes displaying this phenotype in disease models.

• Why it matters: Understanding how astrocytes interact with T cells is crucial because these interactions drive autoimmune processes in the CNS, such as multiple sclerosis, yet their mechanisms remain poorly defined.
• What they did: The study used rabies barcode interaction detection, single-cell RNA sequencing, and genetic perturbation to identify that astrocytes expressing CD40 and MHC-II promote T cell activation and autoimmunity, especially through direct interactions with CD4+ T cells.
• The result: Activation of astrocyte CD40 induces lipid droplet accumulation that supplies acetyl-CoA, promoting NF-κB activation and antigen presentation, revealing a new pathway contributing to CNS autoimmune pathology.