Researchers at Washington University School of Medicine in St. Louis found that blocking the chemokine receptor CXCR3 reduced T-cell infiltration into the brain and limited neurodegeneration in a mouse model of tauopathy, according to a study published September 28 in Neuron.
Mice treated with a peripherally administered anti-CXCR3 antibody had roughly 50% fewer T cells in the brain and retained approximately 40% more tissue in memory-related regions than untreated animals. The treatment also reduced markers of neuronal damage and improved memory performance despite leaving tau tangle levels unchanged.
The researchers found that tau-associated inflammation increased the chemokine CXCL10, which attracts CXCR3-expressing T cells into the brain. Genetic loss of either CXCL10 or CXCR3 prevented T-cell infiltration, while distribution studies showed that the anti-CXCR3 antibody reached the brain border but did not enter brain tissue, indicating that peripheral blockade was sufficient to disrupt the process.
The study builds on earlier work from David Holtzman's group showing that T cells accumulate in tau-rich brain regions and contribute to neurodegeneration. The new findings identify CXCR3-mediated trafficking as a potential intervention point downstream of tau accumulation, suggesting that neurodegeneration might be reduced without directly clearing tau or requiring a therapy to cross the blood-brain barrier.