title: Endothelial IL-1R1 is a critical mediator of EAE pathogenesis.
abstract: Interleukin-1 (IL-1) has been implicated in the disease progression of multiple sclerosis (MS). In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), the induction of disease is significantly attenuated in mice lacking the type I IL-1 receptor (IL-1R1). In this study, we created a transgenic mouse (eIL-1R1 kd) in which IL-1R1 expression is knocked down specifically in endothelial cells. Induction of EAE in eIL-1R1 kd mice results in a decrease in incidence, severity and delayed onset of EAE. In addition, eIL-1R1 kd mice show significant decrease in VCAM-1 expression and diminished CD45(+) and CD3(+) infiltrating leukocytes in the spinal cord in animals challenged with EAE. Further, IL-1 and IL-23 stimulate IL-17 production by splenocytes from both wild type and the eIL-1R1 kd animals. Similarly, IL-1 and IL-23 synergistically stimulate splenocytes proliferation in these two strains of animals. After immunization with MOG(79-96), although eIL-1R1 kd mice displayed greatly reduced clinical scores, their splenocytes produced IL-17 and proliferated in response to a second MOG challenge, similar to wild type animals. These findings indicate a critical role for endothelial IL-1R1 in mediating the pathogenesis of EAE, and describe a new model that can be used to study endothelial IL-1R1.
authors.affiliation: Institute of Behavior Medicine, 3132 Postle Hall, 305 West 12th Avenue, Ohio State University, Columbus, OH 43210-1094, USA.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Li
authors.forename: Nicole
authors.initials: N
authors.lastname: Powell
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Natalya
authors.initials: N
authors.lastname: Belevych
authors.forename: San
authors.initials: S
authors.lastname: Ching
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Sheridan
authors.forename: Caroline
authors.initials: C
authors.lastname: Whitacre
authors.forename: Ning
authors.initials: N
authors.lastname: Quan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007114:Immunization; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology; D053759:Interleukin-23 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D020556:Neutrophil Infiltration; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D053573:Receptors, Interleukin-1 Type I / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D007375:Interleukin-1; D020381:Interleukin-17; D053759:Interleukin-23; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D019010:Vascular Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D017493:Leukocyte Common Antigens