The central role of CXCL10-CXCR3 signaling in neuroinflammation and neuropathology

The role of neuroinflammation is becoming increasingly prominent as our understanding of the mechanisms underlying central nervous system disorders advances. What makes this phenomenon particularly intriguing from a clinical perspective is that neuroinflammation is consistently present, regardless of the specific neuropathology. One of its major consequences is the recruitment of immune cells from the circulation into the brain parenchyma, leading to chronic damage. Therefore, uncovering the molecular mechanisms driving this process may provide valuable therapeutic insights. Among the numerous molecules involved in chemotaxis, growing evidence highlights the key role of CXCL10 and its receptor, CXCR3. CXCL10 is a ubiquitous and well-characterized chemoattractant secreted by all brain-resident cell types, while CXCR3 is strongly expressed by immune and pro-inflammatory cells, such as Th1 lymphocytes and NK cells. This review aims to compile experimental evidence from various pathological contexts to demonstrate that the CXCL10-CXCR3 axis may serve as a therapeutic target for mitigating detrimental events in nervous tissue, potentially improving clinical outcomes in neurodegenerative diseases.