The susceptibility of CXCR3KO mice to EAE is associated with the increased numbers of Th17 infiltrating in CNS (60.4)

Abstract

Abstract CXCR3 and its ligands are highly associated with neuronal inflammation. Given that Th17 cells play a critical role in EAE pathogenesis and that Th17 cells have been shown to express CXCR3, we intended to investigate the effect of CXCR3 on EAE, particularly focusing on Th17 cells. In this study, we demonstrated that CXCR3KO mice developed more severe EAE as compared with wild-type mice. Of interest, CXCR3KO mice exhibited higher numbers of Th17 cells infiltrating in CNS as compared with wild-type mice. In accordance with this result, using the passive EAE model, we showed that mice receiving Th17 cells derived from MOG-immunized CXCR3KO mice developed more severe EAE as compared with mice receiving Th17 cells derived from MOG-immunized wild-type mice. Furthermore, intracellular staining revealed that CXCR3KO mice exhibited the increased numbers of Th17 cells expressing GM-CSF, a recently identified encephalitogenic cytokine that contributes to the effector phase of EAE. Altogether, we provide evidence that CXCR3 plays a protective role rather than a immunopathgenic role in EAE via negative regulation of Th17 cells infiltrating in CNS. The mechanism underlying the increased numbers of Th17 cells infiltrating in CNS of CXCR3KO mice leading to the susceptibility to EAE is currently under investigation.