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Review

Role of CXCL10 in central nervous system inflammation

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Pages 1-18 | Published online: 27 Feb 2014

Figures & data

Figure 1 Chemokine receptor CXCR3 and its ligands CXCL9, CXCL10, and CXCL11. CXCR3 is a seven transmembrane G-protein coupled receptor. The DRY-motif is critical for engaging with cytoplasmic G-proteins to initiate signaling. CXCR3 binds three different ligands, ie, CXCL9, CXCL10, and CXCL11. These ligands bind to specific and distinct regions within the receptor.

Figure 1 Chemokine receptor CXCR3 and its ligands CXCL9, CXCL10, and CXCL11. CXCR3 is a seven transmembrane G-protein coupled receptor. The DRY-motif is critical for engaging with cytoplasmic G-proteins to initiate signaling. CXCR3 binds three different ligands, ie, CXCL9, CXCL10, and CXCL11. These ligands bind to specific and distinct regions within the receptor.

Table 1 Medically important neurotropic pathogens

Table 2 Role of CXCL10 in autoimmunity and infection of the CNS has been studied using both CXCL10 null mice and a neutralizing antibody

Figure 2 CXCL10 function can be either beneficial or detrimental to the host depending on the disease and context. Diseases of autoimmunity and neurodegeneration tend to be more severe in animals with a functioning CXCL10-CXCR3 axis. In contrast, the role of CXCL10 can be either beneficial or detrimental to the host during CNS infection. For example, during cerebral malaria, CXCL10 promotes a damaging infiltrate of leukocytes that does not appear to aid pathogen clearance. In comparison, CXCL10-driven responses to HSV appear protective by facilitating the entry of leukocytes that enhance pathogen clearance.

Abbreviations: EAE, experimental autoimmune encephalomyelitis; MS, multiple sclerosis; MHV, mouse hepatitis virus; LCMV, lymphocytic choriomeningitis virus; WNV, West Nile virus; HSV, herpes simplex virus.
Figure 2 CXCL10 function can be either beneficial or detrimental to the host depending on the disease and context. Diseases of autoimmunity and neurodegeneration tend to be more severe in animals with a functioning CXCL10-CXCR3 axis. In contrast, the role of CXCL10 can be either beneficial or detrimental to the host during CNS infection. For example, during cerebral malaria, CXCL10 promotes a damaging infiltrate of leukocytes that does not appear to aid pathogen clearance. In comparison, CXCL10-driven responses to HSV appear protective by facilitating the entry of leukocytes that enhance pathogen clearance.

Table 3 Summary of small molecule inhibitors that have been used to modulate CXCL10 function