综述：CXCL10 - CXCR3信号在神经炎症和神经病理中的核心作用

这篇综述指出神经炎症在神经系统疾病机制研究中愈发重要，CXCL10及其受体CXCR3在免疫细胞招募致脑慢性损伤中起关键作用，该信号轴有望成为治疗靶点改善神经退行性疾病临床结局。

　　

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.

The central nervous system (CNS) has long been considered an immune - privileged compartment due to the presence of the blood - brain barrier (BBB). The BBB is a multicellular structure composed of endothelial cells, pericytes, astrocytes, neurons, and microglial cells, which collectively act as a barrier to prevent the undesired infiltration of peripheral immune cells into the cerebral parenchyma [1], [2]. However, the immune - privileged status of the CNS is not absolute, as various physiological processes can disrupt this barrier and allow immune cells to enter the CNS.

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.

Based on the evidence presented in this review, it is evident that the CXCL10 - CXCR3 axis represents a pivotal element in the pathogenesis of CNS disorders. In the era of targeted molecular therapy, identifying a novel therapeutic target—whose central role has been independently validated by multiple laboratories across a wide range of models—opens new avenues for the development of innovative treatments for diseases whose underlying causes remain only partially understood.

This study was financially supported by the University of Antwerp (BOF - GOA ID 41739 and BOF - Sabbat ID 50389) and the Fund for Scientific Research Flanders (FWO - Sabbat ID K800224N), all granted to PP.

Alexandro A. Bufi obtained his Bachelor’s degree in Medical and Pharmaceutical Biotechnology from the University of Bari Aldo Moro, followed by a Master’s degree in Biotechnology for Personalized Medicine from the Università Cattolica del Sacro Cuore in Rome. He is currently a PhD student in Experimental and Translational Medicine at Università Cattolica del Sacro Cuore under the supervision of Professor Ornella Parolini, and a joint PhD student in Medical Sciences at the University of...

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Peter Ponsaerts reports financial support was provided by Research Foundation Flanders. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.