Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune encephalomyelitis in mice.
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.
['Ahn|Bum Ju|BJ|', 'Le|Hoang|H|', 'Shin|Min Wook|MW|', 'Bae|Sung-Jin|SJ|', 'Lee|Eun Ji|EJ|', 'Wee|Hee-Jun|HJ|', 'Cha|Jong-Ho|JH|', 'Lee|Hyo-Jong|HJ|', 'Lee|Hye Shin|HS|', 'Kim|Jeong Hun|JH|', 'Kim|Chang-Yeon|CY|', 'Seo|Ji Hae|JH|', 'Lo|Eng H|EH|', 'Jeon|Sejin|S|', 'Lee|Mi-Ni|MN|', 'Oh|Goo Taeg|GT|', 'Yin|Guo Nan|GN|', 'Ryu|Ji-Kan|JK|', 'Suh|Jun-Kyu|JK|', 'Kim|Kyu-Won|KW|']
D000818:Animals D057134:Antibodies, Neutralizing D001854:Bone Marrow Cells D015816:Cell Adhesion Molecules, Neuronal D002460:Cell Line D002465:Cell Movement D004198:Disease Susceptibility D004681:Encephalomyelitis, Autoimmune, Experimental D008264:Macrophages D051379:Mice D018345:Mice, Knockout D009103:Multiple Sclerosis D009414:Nerve Growth Factors
Ninjurin1 Autoimmunity Leukocyte Leukocyte Trafficking EAE Multiple Sclerosis Inflammation Transendothelial Migration Autoimmune Diseases