CX3CR1 Expression Is Required for the Development of Pain like Behavior in a Mouse Model of Autoimmune Peripheral Neuropathy

Abstract

POSTER ABSTRACTIntroduction/Aim: Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are prototypic autoimmune peripheral neuropathy (APN) which represent a serious neurological emergency. Although current treatment options have proven effective, many patients still present with a severe disease course, pain and residual deficits. We have reported that B7.2 transgenic L31 mice spontaneously develop inflammatory peripheral neuropathy. We also showed that an injury to peripheral nerve in L31 mice facilitates the development of APN. Both effector/memory CD8 T cells and B7.2+ macrophages are required for disease initiation. Here, we highlighted the importance of CX3CR1 expression in disease pathogenesis and in the development of pain like behavior in L31 mice.Methods: L31 mice were crossed with CX3CR1KO mice, and the effect on macrophage phagocytic ability, activated CD8 T cells function and pathology were assessed.Results: CX3CR1 expression was strongly upregulated in sciatic nerve of symptomatic L31 mice which correlated with increased phagocytic ability. Enhanced phagocytosis in L31 mice was impeded in L31/CX3CR1−/- mice. Also, injury failed to trigger APN in L31 mice deficient of CX3CR1 expression. APN associated sensory deficits positively correlated with the amount of CX3CR1 expression. In addition, CX3CR1 deficiency led to a high number of dying monocytes, macrophages and activated CD8 T cells suggesting that CX3CR1 signaling may be crucial for their survival. Lastly, sciatic nerve histology showed no myelin and axon damage in L31/CX3CR1−/- mice.Discussion/Conclusions: These data suggest that CX3CR1 expression are critical for the development of APN in L31 mice. CX3CR1 expressing macrophages contribute to disease pathogenesis via enhanced antigen phagocytosis and presentation.