Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Modulates Experimental Autoimmune Encephalomyelitis via an iNKT Cell-Dependent Mechanism
AUTOR(ES)
Fujita, Mayumi
FONTE
American Society for Investigative Pathology
RESUMO
Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a CEA family member that has been reported to have an important role in the regulation of Th1-mediated colitis. In this study, we examined the role of CEACAM1 in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Treatment of C57BL/6J mice with CEACAM1-Fc fusion protein, a homophilic ligand of CEACAM1, inhibited the severity of EAE and reduced myelin oligodendrocyte glycoprotein-derived peptide (MOG35–55)-reactive interferon-γ and interleukin-17 production. In contrast, treatment of these animals with AgB10, an anti-mouse CEACAM1 blocking monoclonal antibody, generated increased severity of EAE in association with increased MOG35–55-specific induction of both interferon-γ and interleukin-17. These results indicated that the signal elicited through CEACAM1 ameliorated EAE disease severity. Furthermore, we found that there was both a rapid and enhanced expression of CEACAM1 on invariant natural killer T cells after activation. The effect of CEACAM1-Fc fusion protein and anti-CEACAM1 mAb on both EAE and MOG35–55-reactive cytokine responses were abolished in invariant natural killer T cell–deficient Jα18−/− mice. Taken together, the ligation of CEACAM1 negatively regulates the severity of EAE by reducing MOG35–55-specific induction of both interferon-γ and interleukin-17 via invariant natural killer T cell-dependent mechanisms.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2731130Documentos Relacionados
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