title: Intracranial delivery of interleukin-17A via adeno-associated virus fails to induce physical and learning disabilities and neuroinflammation in mice but improves glucose metabolism through AKT signaling pathway.
abstract: Interleukin-17A (IL-17A) is generally considered as one of the pathogenic factors involved in multiple sclerosis (MS). Indirect evidence for this is that IL-17A-producing T helper 17 (Th17) cells preferentially accumulate in lesions of MS and experimental autoimmune encephalomyelitis (EAE). However, a direct involvement of IL-17A in MS pathogenesis is still an open question. In this study, we overexpressed IL-17A in the brains of mice (IL-17A-in-Brain mice) via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated gene delivery. In spite of high levels of IL-17A expression in the brain and blood, IL-17A-in-Brain mice exhibit no inflammatory responses and no abnormalities in motor coordination and spatial orientation. Unexpectedly, IL-17A-in-Brain mice show decreases in body weight and adipose tissue mass and an improvement in glucose tolerance and insulin sensitivity. IL-17A enhances glucose uptake in PC12 cells by activation of AKT. Our results provide direct evidence for the first time that IL-17A overexpression in the central nervous system does not cause physical and learning disabilities and neuroinflammation and suggest that IL-17A may regulate glucose metabolism through the AKT signaling pathway.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
authors.forename: Junling
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Lim
authors.affiliation: Department of Psychology, University of Rouen, Rouen, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA. Electronic address: kfukuchi@uic.edu.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Fukuchi
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018014:Gene Transfer Techniques; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D020381:Interleukin-17 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D007859:Learning Disabilities / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: AKT; Adipose tissues; Experimental autoimmune encephalomyelitis; Glucose tolerance; IL-17A; Insulin sensitivity; Motor activity; Motor coordination; Multiple sclerosis; Neuroinflammation