Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Modulates Experimental Autoimmune Encephalomyelitis via an iNKT Cell-Dependent Mechanism

Mayumi Fujita^*, Takao Otsuka^*, Miho Mizuno^*, Chiharu Tomi^*, Takashi Yamamura^* and Sachiko Miyake^*

From the Department of Immunology,^* National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo; and the Third Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan

Carcinoembryonic antigen-related cellular adhesion molecule1 (CEACAM1) is a CEA family member that has been reported tohave an important role in the regulation of Th1-mediated colitis.In this study, we examined the role of CEACAM1 in an animalmodel 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 EAEand reduced myelin oligodendrocyte glycoprotein-derived peptide(MOG_35–55)-reactive interferon- ${gamma}$ and interleukin-17 production.In contrast, treatment of these animals with AgB10, an anti-mouseCEACAM1 blocking monoclonal antibody, generated increased severityof EAE in association with increased MOG_35–55-specificinduction of both interferon- ${gamma}$ and interleukin-17. These resultsindicated that the signal elicited through CEACAM1 amelioratedEAE disease severity. Furthermore, we found that there was botha rapid and enhanced expression of CEACAM1 on invariant naturalkiller T cells after activation. The effect of CEACAM1-Fc fusionprotein and anti-CEACAM1 mAb on both EAE and MOG_35–55-reactivecytokine responses were abolished in invariant natural killerT cell–deficient J ${alpha}$ 18^–/– mice. Taken together,the ligation of CEACAM1 negatively regulates the severity ofEAE by reducing MOG_35–55-specific induction of both interferon- ${gamma}$ and interleukin-17 via invariant natural killer T cell-dependentmechanisms.