title: Impaired dendritic cell function in a spontaneous autoimmune polyneuropathy.
abstract: Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout NOD mice mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy, and is mediated by myelin protein zero (P0)-reactive Th1 cells. In this study, we focused on the effect of B7-2 deletion on the function of dendritic cells (DCs) within the context of SAP. We found that development of SAP was associated with a preponderance or increase of CD11b(+) DCs in peripheral lymph nodes and sciatic nerves. B7-2 deletion led to altered immunophenotypic properties that differ between CD11b(+) DCs and CD8α(+) DCs. Both DC subsets from B7-2 knockout NOD mice exhibited impaired capacity to capture fluorophore-labeled myelin P0, but diminished Ag-presenting function was observed only in CD11b(+) DCs. Clinical assessment, electrophysiologic studies, and splenocyte proliferation studies revealed that absence of B7-2 on DCs was sufficient to cause impaired ability to induce tolerance to P0, which could be overcome by preconditioning with IL-10. Tolerance induction by Ag-pulsed wild-type NOD DCs was dependent on IL-10 and was associated with increased CD4(+) regulatory T cells, whereas tolerance induction by IL-10-conditioned B7-2-deficient DCs was associated with increased percentages of both regulatory T cells and B10 cells in the spleen. We conclude that B7-2 deletion has an impact on the distribution of DC subsets in lymphoid organs and alters the expression of costimulatory molecules, but functional consequences are not uniform across DC subsets. Defective tolerance induction in the absence of B7-2 can be restored by preconditioning of DCs with IL-10.
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Songhua
authors.initials: S
authors.lastname: Quan
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637; and Department of Pathology, Inje University School of Medicine, Busan 614-735, Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Danuta
authors.initials: D
authors.lastname: Dukala
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637; and bsoliven@neurology.bsd.uchicago.edu.
authors.forename: Betty
authors.initials: B
authors.lastname: Soliven
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D011115:Polyneuropathies / Q000276:immunology* / Q000473:pathology
chemical_list: D016753:Interleukin-10
references.citation: Immunity. 2003 Jun;18(6):801-11
references.pmid: 12818161
references.citation: J Immunol. 2004 Sep 15;173(6):3631-9
references.pmid: 15356107
references.citation: J Clin Invest. 2004 Oct;114(7):979-87
references.pmid: 15467837
references.citation: J Immunol. 2008 Nov 15;181(10):6923-33
references.pmid: 18981112
references.citation: Immunol Rev. 2010 Mar;234(1):317-34
references.pmid: 20193028
references.citation: J Exp Med. 2002 Jul 15;196(2):217-27
references.pmid: 12119346
references.citation: PLoS One. 2014;9(1):e83575
references.pmid: 24465383
references.citation: Clin Exp Immunol. 2014 Feb;175(2):181-91
references.pmid: 24116957
references.citation: Nat Immunol. 2007 Feb;8(2):172-80
references.pmid: 17206145
references.citation: Eur J Immunol. 1999 Oct;29(10):3140-7
references.pmid: 10540325
references.citation: J Immunol. 2006 Sep 1;177(5):2948-58
references.pmid: 16920930
references.citation: Blood. 2010 Aug 12;116(6):935-44
references.pmid: 20448110
references.citation: J Immunol. 2008 Dec 15;181(12):8753-60
references.pmid: 19050296
references.citation: Immunity. 2008 May;28(5):639-50
references.pmid: 18482568
references.citation: J Neuroimmunol. 2014 Apr 15;269(1-2):28-37
references.pmid: 24565076
references.citation: J Biol Chem. 2002 Mar 8;277(10):7766-75
references.pmid: 11726649
references.citation: Transpl Immunol. 2009 Jan;20(3):171-9
references.pmid: 18848987
references.citation: J Exp Med. 2002 Mar 4;195(5):603-16
references.pmid: 11877483
references.citation: Immunity. 2008 Dec 19;29(6):986-97
references.pmid: 19062318
references.citation: Front Immunol. 2013 May 31;4:129
references.pmid: 23755052
references.citation: J Immunol. 2008 Aug 15;181(4):2483-93
references.pmid: 18684939
references.citation: Front Immunol. 2014 Jan 31;5:7
references.pmid: 24550907
references.citation: J Exp Med. 2001 Sep 3;194(5):677-84
references.pmid: 11535635
references.citation: Acta Neuropathol Commun. 2014;2:5
references.pmid: 24401681
references.citation: J Exp Med. 2009 Mar 16;206(3):549-59
references.pmid: 19237601
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1036-41
references.pmid: 9927689
references.citation: J Exp Med. 2003 Jul 21;198(2):235-47
references.pmid: 12874257
references.citation: Nat Immunol. 2002 Nov;3(11):1097-101
references.pmid: 12368911
references.citation: J Exp Med. 2010 Aug 30;207(9):1891-905
references.pmid: 20696698
references.citation: J Autoimmun. 2002 Aug-Sep;19(1-2):23-35
references.pmid: 12367556
references.citation: J Exp Med. 2002 Oct 21;196(8):1099-104
references.pmid: 12391021
references.citation: Eur J Immunol. 2009 Nov;39(11):3084-90
references.pmid: 19757438
references.citation: J Exp Med. 2009 Mar 16;206(3):507-14
references.pmid: 19221395
references.citation: Clin Immunol Immunopathol. 1997 May;83(2):117-26
references.pmid: 9143372
references.citation: J Immunol. 1993 Mar 15;150(6):2534-43
references.pmid: 8450229
references.citation: J Immunol. 2000 Mar 1;164(5):2444-56
references.pmid: 10679081
references.citation: J Immunol. 2005 Nov 1;175(9):5649-55
references.pmid: 16237054
references.citation: J Neuroimmunol. 2009 Sep 29;214(1-2):93-100
references.pmid: 19647880
references.citation: Transpl Immunol. 2003 Jul-Sep;11(3-4):245-58
references.pmid: 12967778
references.citation: J Immunol. 1998 Oct 1;161(7):3299-306
references.pmid: 9759845
references.citation: Immunity. 2000 Apr;12(4):431-40
references.pmid: 10795741
references.citation: J Immunol. 2007 May 15;178(10):6236-41
references.pmid: 17475851
references.citation: J Immunol. 2006 Aug 15;177(4):2365-72
references.pmid: 16887998
references.citation: Science. 2011 Apr 29;332(6029):600-3
references.pmid: 21474713
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: J Exp Med. 1999 Feb 1;189(3):587-92
references.pmid: 9927520
references.citation: Cell Immunol. 2002 Feb;215(2):162-72
references.pmid: 12202153
references.citation: Clin Immunol. 2012 Mar;142(3):332-42
references.pmid: 22225835
references.citation: Clin Immunol. 2011 Jun;139(3):336-49
references.pmid: 21458378
references.citation: J Immunol. 2007 Oct 15;179(8):5041-53
references.pmid: 17911589
references.citation: Nat Rev Immunol. 2002 Feb;2(2):116-26
references.pmid: 11910893
references.citation: Diabetes Care. 2011 Sep;34(9):2026-32
references.pmid: 21680720
references.citation: J Exp Med. 2005 Jan 3;201(1):127-37
references.pmid: 15630140
references.citation: J Neuroimmunol. 2005 Feb;159(1-2):165-76
references.pmid: 15652416
references.citation: J Immunol. 1997 Nov 15;159(10):4772-80
references.pmid: 9366401
references.citation: Immunity. 2000 Oct;13(4):453-62
references.pmid: 11070164
references.citation: Nat Immunol. 2004 Nov;5(11):1134-42
references.pmid: 15467723
references.citation: Blood. 2001 Sep 1;98(5):1512-23
references.pmid: 11520802
references.citation: J Immunol. 2001 Aug 1;167(3):1461-8
references.pmid: 11466366
references.citation: Nat Immunol. 2009 Feb;10(2):167-75
references.pmid: 19098919
references.citation: Mol Ther. 2014 Jul;22(7):1353-63
references.pmid: 24762627
references.citation: J Immunol. 2005 May 15;174(10):6440-8
references.pmid: 15879146