Carcinoembryonic antigen-related cell adhesion molecule 1 modulates experimental autoimmune encephalomyelitis via an iNKT cell-dependent mechanism.
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.
Fujita
Mayumi
M
Department of Immunology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
Otsuka
Takao
T
Mizuno
Miho
M
Tomi
Chiharu
C
Yamamura
Takashi
T
Miyake
Sachiko
S
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
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
Mol Microbiol. 1997 Dec;26(5):971-80
9426134
Nat Rev Neurosci. 2002 Apr;3(4):291-301
11967559
Histochemistry. 1990;94(2):179-86
2193005
Nat Rev Immunol. 2006 Jun;6(6):433-46
16724098
Am J Pathol. 2008 Dec;173(6):1714-23
18974295
Nat Med. 2007 Apr;13(4):423-31
17384649
Nature. 2003 Feb 13;421(6924):744-8
12610626
J Immunol. 2001 Jun 1;166(11):6537-44
11359805
J Exp Med. 2004 Jul 5;200(1):79-87
15238607
J Exp Med. 2004 Feb 16;199(4):471-82
14970176
Nat Immunol. 2002 Mar;3(3):229-36
11850628
Cell Microbiol. 2001 Jan;3(1):33-44
11207618
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6238-43
19325124
J Virol. 1997 Apr;71(4):3129-37
9060676
Brain. 2006 Aug;129(Pt 8):1984-92
16835249
J Immunol. 1999 Nov 15;163(10):5278-86
10553050
J Immunol. 2000 Mar 1;164(5):2759-68
10679118
Neuron. 1999 Nov;24(3):511-4
10595504
Nat Med. 2008 Mar;14(3):337-42
18278054
Mol Microbiol. 2001 Feb;39(4):850-62
11251807
Mol Microbiol. 2000 May;36(4):784-95
10844667
Annu Rev Immunol. 2007;25:297-336
17150027
J Immunol. 2004 Mar 15;172(6):3544-52
15004155
Eur J Immunol. 1998 Nov;28(11):3664-74
9842909
Curr Opin Neurobiol. 1993 Oct;3(5):779-84
8260829
Int Rev Immunol. 2007 Jan-Apr;26(1-2):73-94
17454265
Nat Med. 2007 Feb;13(2):139-45
17290272
Annu Rev Immunol. 2005;23:683-747
15771584
Mol Microbiol. 1996 Dec;22(5):941-50
8971715
J Immunol. 2006 Jul 1;177(1):566-73
16785554
J Clin Invest. 2001 Sep;108(5):739-47
11544280
Mol Microbiol. 2004 May;52(4):963-83
15130118
J Immunol. 2004 Mar 15;172(6):3535-43
15004154
J Immunol. 1999 Aug 1;163(3):1363-70
10415036
Oncogene. 1999 Sep 30;18(40):5563-72
10523833
Annu Rev Immunol. 2005;23:877-900
15771592
J Histochem Cytochem. 1996 Jan;44(1):35-41
8543780
J Exp Med. 2008 Jul 7;205(7):1535-41
18573909
Eur J Immunol. 1996 Jul;26(7):1641-6
8766573
J Immunol. 1996 Oct 15;157(8):3223-7
8871615
Nat Immunol. 2007 Apr;8(4):345-50
17375096
Nature. 2001 Oct 4;413(6855):531-4
11586362
Semin Cancer Biol. 1999 Apr;9(2):67-81
10202129
Nature. 2007 Jul 26;448(7152):484-487
17581588
J Immunol. 2002 Feb 1;168(3):1028-35
11801635
J Clin Invest. 2002 Oct;110(7):943-53
12370272