| First Author | Döring A | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 3 | Pages | 813-21 |
| PubMed ID | 21341265 | Mgi Jnum | J:175419 |
| Mgi Id | MGI:5285503 | Doi | 10.1002/eji.201040912 |
| Citation | Doring A, et al. (2011) TET inducible expression of the alpha4beta7-integrin ligand MAdCAM-1 on the blood-brain barrier does not influence the immunopathogenesis of experimental autoimmune encephalomyelitis. Eur J Immunol 41(3):813-21 |
| abstractText | Inhibiting the alpha4 subunit of the integrin heterodimers alpha4beta1 and alpha4beta7 with the mab natalizumab is an effective treatment of multiple sclerosis (MS). Which of the two alpha4 heterodimers is involved in disease pathogenesis has, however, remained controversial. Whereas the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is ameliorated in beta7-integrin-deficient C57BL/6 mice, neutralizing antibodies against the beta7-integrin subunit or the alpha4beta7-integrin heterodimer fail to interfere with EAE pathogenesis in the SJL mouse. To facilitate alpha4beta7-integrin-mediated immune-cell trafficking across the blood-brain barrier (BBB), we established transgenic C57BL/6 mice with endothelial cell-specific, inducible expression of the alpha4beta7-integrin ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 using the tetracycline (TET)-OFF system. Although TET-regulated MAdCAM-1 induced alpha4beta7-integrin mediated interaction of alpha4beta7(+) /alpha4beta1(-) T cells with the BBB in vitro and in vivo, it failed to influence EAE pathogenesis in C57BL/6 mice. TET-regulated MAdCAM-1 on the BBB neither changed the localization of central nervous system (CNS) perivascular inflammatory cuffs nor did it enhance the percentage of alpha4beta7-integrin(+) inflammatory cells within the CNS during EAE. In conclusion, our study demonstrates that ectopic expression of MAdCAM-1 at the BBB does not increase alpha4beta7-integrin-mediated immune cell trafficking into the CNS during MOG(aa35-55)-induced EAE. |
