title: Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune encephalomyelitis in mice.
abstract: Ninjurin1 is a homotypic adhesion molecule that contributes to leukocyte trafficking in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, in vivo gene deficiency animal studies have not yet been done. Here, we constructed Ninjurin1 knock-out (KO) mice and investigated the role of Ninjurin1 on leukocyte trafficking under inflammation conditions such as EAE and endotoxin-induced uveitis. Ninjurin1 KO mice attenuated EAE susceptibility by reducing leukocyte recruitment into the injury regions of the spinal cord and showed less adhesion of leukocytes on inflamed retinal vessels in endotoxin-induced uveitis mice. Moreover, the administration of a custom-made antibody (Ab26-37) targeting the Ninjurin1 binding domain ameliorated the EAE symptoms, showing the contribution of its adhesion activity to leukocyte trafficking. In addition, we addressed the transendothelial migration (TEM) activity of bone marrow-derived macrophages and Raw264.7 cells according to the expression level of Ninjurin1. TEM activity was decreased in Ninjurin1 KO bone marrow-derived macrophages and siNinj1 Raw264.7 cells. Consistent with this, GFP-tagged mNinj1-overexpressing Raw264.7 cells increased their TEM activity. Taken together, we have clarified the contribution of Ninjurin1 to leukocyte trafficking in vivo and delineated its direct functions to TEM, emphasizing Ninjurin1 as a beneficial therapeutic target against inflammatory diseases such as multiple sclerosis.
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences and.
authors.forename: Bum Ju
authors.initials: BJ
authors.lastname: Ahn
authors.forename: Hoang
authors.initials: H
authors.lastname: Le
authors.forename: Min Wook
authors.initials: MW
authors.lastname: Shin
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Bae
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Wee
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Hyo-Jong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hye Shin
authors.initials: HS
authors.lastname: Lee
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Chang-Yeon
authors.initials: CY
authors.lastname: Kim
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Seo
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Sejin
authors.initials: S
authors.lastname: Jeon
authors.forename: Mi-Ni
authors.initials: MN
authors.lastname: Lee
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Guo Nan
authors.initials: GN
authors.lastname: Yin
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; C484439:Ninj1 protein, mouse
keywords: Autoimmune Diseases; Autoimmunity; EAE; Inflammation; Leukocyte; Leukocyte Trafficking; Multiple Sclerosis; Ninjurin1; Transendothelial Migration