Upregulation of autophagy related genes in the dorsal root ganglion in CD137L KO mice, link to peripheral nerve injury induced-peripheral neuropathy 2254504

Abstract Introduction CD137 Ligand (CD137L, AKA: 4-1BBL) is a co-stimulatory molecule facilitating the activation and function of adaptive immunity. Previously we have demonstrated that CD137L knockout (KO) mice display reduced pain-like behaviors and faster recovery following peripheral nerve injury. Autophagy is a cellular process to facilitate the selective degradation and recycling of cytoplasmic contents, playing a critical cellular function in maintaining intracellular homeostasis. Increasing studies have shown the contribution of the protective effects of enhanced autophagic activities to pain-like behaviors following peripheral nerve injury. Here we examined the potential association between autophagic activities and CD137L depletion mediated pro-nociception. Methods RNA profiling on several autophagy related genes was performed via a NanoString assay in both lumbar spinal cord (LSC) and dorsal root ganglion (DRG) tissues harvested from CD137L KO mice and corresponding wild type (WT) controls. Results An overall upregulation of autophagy related genes was observed, more so in the DRGs than in the LSC, at basal levels in CD137L KO mice compared to WT mice. Particularly, we detected a significant upregulation of DRG EPG5, ectopic P-granules 5 autophagy tethering factor, a protein facilitating the fusion between autophagosomes and lysosomes. Follow-up qRT-PCR verified the upregulation of EPG5 and showed the upregulation of genes encoding EPG5’s binding partners, LC3 and Rab7, at both basal level and 14 days following sciatic nerve crush in CD137L KO mice vs. WT controls. Assessment of these autophagy factors at protein levels is on-going. Conclusion Our current results support the potential contribution of enhanced autophagic activities to reduced pain-like behaviors in CD137L KO mice. Funding Source NIH/NINDS 1R01NS098426 (PI Cao). Topic Categories Immune Mechanisms of Human Disease (HUM)