CX3CL1 (fractalkine)-CX3CR1 interface drives CD8⁺ T cell-induced neurodegeneration in human brain organoids.

CX3CL1-CX3CR1 interaction drives CD8⁺ T cell-induced neurodegeneration in human brain organoids, with increased neuronal injury markers observed.

• Why it matters: Understanding how immune cells contribute to neurodegeneration is crucial for developing targeted therapies for diseases like Alzheimer's, where immune-neuron interactions are implicated but not fully understood.
• What they did: Researchers used human cortical organoids exposed to amyloid-β to study CD8⁺ T cell responses, demonstrating that Aβ increases CX3CL1 expression and recruits CX3CR1⁺ CD8⁺ T cells, which then induce neuronal damage.
• The result: Blocking CD8⁺ T cell cytokines and cytotoxic molecules rescued neuronal injury, highlighting the CX3CL1-CX3CR1 axis and T cell effector programs as potential therapeutic targets in immune-driven neurodegeneration.