title: Carcinoembryonic antigen-related cell adhesion molecule 1 modulates experimental autoimmune encephalomyelitis via an iNKT cell-dependent mechanism.
abstract: 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 (MOG(35-55))-reactive interferon-gamma 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 MOG(35-55)-specific induction of both interferon-gamma 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 MOG(35-55)-reactive cytokine responses were abolished in invariant natural killer T cell-deficient Jalpha18(-/-) mice. Taken together, the ligation of CEACAM1 negatively regulates the severity of EAE by reducing MOG(35-55)-specific induction of both interferon-gamma and interleukin-17 via invariant natural killer T cell-dependent mechanisms.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Takao
authors.initials: T
authors.lastname: Otsuka
authors.forename: Miho
authors.initials: M
authors.lastname: Mizuno
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D006023:Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D055611:Natural Killer T-Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D019138:Antibodies, Blocking; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D006023:Glycoproteins; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma
references.citation: Mol Microbiol. 1997 Dec;26(5):971-80
references.pmid: 9426134
references.citation: Nat Rev Neurosci. 2002 Apr;3(4):291-301
references.pmid: 11967559
references.citation: Histochemistry. 1990;94(2):179-86
references.pmid: 2193005
references.citation: Nat Rev Immunol. 2006 Jun;6(6):433-46
references.pmid: 16724098
references.citation: Am J Pathol. 2008 Dec;173(6):1714-23
references.pmid: 18974295
references.citation: Nat Med. 2007 Apr;13(4):423-31
references.pmid: 17384649
references.citation: Nature. 2003 Feb 13;421(6924):744-8
references.pmid: 12610626
references.citation: J Immunol. 2001 Jun 1;166(11):6537-44
references.pmid: 11359805
references.citation: J Exp Med. 2004 Jul 5;200(1):79-87
references.pmid: 15238607
references.citation: J Exp Med. 2004 Feb 16;199(4):471-82
references.pmid: 14970176
references.citation: Nat Immunol. 2002 Mar;3(3):229-36
references.pmid: 11850628
references.citation: Cell Microbiol. 2001 Jan;3(1):33-44
references.pmid: 11207618
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6238-43
references.pmid: 19325124
references.citation: J Virol. 1997 Apr;71(4):3129-37
references.pmid: 9060676
references.citation: Brain. 2006 Aug;129(Pt 8):1984-92
references.pmid: 16835249
references.citation: J Immunol. 1999 Nov 15;163(10):5278-86
references.pmid: 10553050
references.citation: J Immunol. 2000 Mar 1;164(5):2759-68
references.pmid: 10679118
references.citation: Neuron. 1999 Nov;24(3):511-4
references.pmid: 10595504
references.citation: Nat Med. 2008 Mar;14(3):337-42
references.pmid: 18278054
references.citation: Mol Microbiol. 2001 Feb;39(4):850-62
references.pmid: 11251807
references.citation: Mol Microbiol. 2000 May;36(4):784-95
references.pmid: 10844667
references.citation: Annu Rev Immunol. 2007;25:297-336
references.pmid: 17150027
references.citation: J Immunol. 2004 Mar 15;172(6):3544-52
references.pmid: 15004155
references.citation: Eur J Immunol. 1998 Nov;28(11):3664-74
references.pmid: 9842909
references.citation: Curr Opin Neurobiol. 1993 Oct;3(5):779-84
references.pmid: 8260829
references.citation: Int Rev Immunol. 2007 Jan-Apr;26(1-2):73-94
references.pmid: 17454265
references.citation: Nat Med. 2007 Feb;13(2):139-45
references.pmid: 17290272
references.citation: Annu Rev Immunol. 2005;23:683-747
references.pmid: 15771584
references.citation: Mol Microbiol. 1996 Dec;22(5):941-50
references.pmid: 8971715
references.citation: J Immunol. 2006 Jul 1;177(1):566-73
references.pmid: 16785554
references.citation: J Clin Invest. 2001 Sep;108(5):739-47
references.pmid: 11544280
references.citation: Mol Microbiol. 2004 May;52(4):963-83
references.pmid: 15130118
references.citation: J Immunol. 2004 Mar 15;172(6):3535-43
references.pmid: 15004154
references.citation: J Immunol. 1999 Aug 1;163(3):1363-70
references.pmid: 10415036
references.citation: Oncogene. 1999 Sep 30;18(40):5563-72
references.pmid: 10523833
references.citation: Annu Rev Immunol. 2005;23:877-900
references.pmid: 15771592
references.citation: J Histochem Cytochem. 1996 Jan;44(1):35-41
references.pmid: 8543780
references.citation: J Exp Med. 2008 Jul 7;205(7):1535-41
references.pmid: 18573909
references.citation: Eur J Immunol. 1996 Jul;26(7):1641-6
references.pmid: 8766573
references.citation: J Immunol. 1996 Oct 15;157(8):3223-7
references.pmid: 8871615
references.citation: Nat Immunol. 2007 Apr;8(4):345-50
references.pmid: 17375096
references.citation: Nature. 2001 Oct 4;413(6855):531-4
references.pmid: 11586362
references.citation: Semin Cancer Biol. 1999 Apr;9(2):67-81
references.pmid: 10202129
references.citation: Nature. 2007 Jul 26;448(7152):484-487
references.pmid: 17581588
references.citation: J Immunol. 2002 Feb 1;168(3):1028-35
references.pmid: 11801635
references.citation: J Clin Invest. 2002 Oct;110(7):943-53
references.pmid: 12370272