The article investigats the role of astrocytes at the border of a central nervous system injury, specifically after a stroke. The key finding is that interferon-responsive astrocytes (IRRAs), identified by high expression of the protein BST2 (bone marrow stromal cell antigen 2), accumulate at the lesion border and drive microglial recruitment and activation. Mechanistically, BST2 promotes the activation of the NF-κB pathway via PKCβII phosphorylation, leading to the secretion of C3, which subsequently engages the microglial C3aR to mediate harmful astrocyte-microglia crosstalk. Genetic or antibody blockade of BST2 reduces these interactions, diminishing microglial activation and improving early motor function and neuronal survival, thus identifying BST2 as a potential therapeutic target for stroke recovery.

References:

• Zhang S, Yuan M, Zhou J, et al. BST2 expression at astrocyte borders promotes microglial recruitment via the C3/C3aR signaling[J]. Neuron, 2025.