title: E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis.
abstract: Dendritic cells (DCs) play a pivotal role in controlling the balance between tolerance and immunity in the intestine. Gut conditioned CD103(+) DCs promote regulatory T (Treg) cell responses; however, little is known about DCs that drive inflammation in the intestine. Here, we show that monocyte-derived inflammatory DCs that express E-cadherin, the receptor for CD103, promote intestinal inflammation. E-cadherin(+) DCs accumulated in the inflamed mesenteric lymph nodes and colon, had high expression of toll-like receptors, and produced colitogenic cytokines, such as IL-6 and IL-23, after activation. Importantly, adoptive transfer of E-cadherin(+) DCs into T cell-restored immunodeficient hosts increased Th17 cell responses in the intestine and led to exacerbation of colitis. These results identify a monocyte-derived inflammatory DC subset that is associated with the pathogenesis of intestinal inflammation, providing a therapeutic target for the treatment of inflammatory bowel disease.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, UK.
authors.forename: Karima R R
authors.initials: KR
authors.lastname: Siddiqui
authors.forename: Sophie
authors.initials: S
authors.lastname: Laffont
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D015820:Cadherins / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039521:CD11c Antigen; D015820:Cadherins; D039001:Integrin alpha Chains; C091367:alpha E integrins
references.citation: Blood. 2000 Dec 15;96(13):4276-84
references.pmid: 11110702
references.citation: Immunity. 2007 Apr;26(4):519-31
references.pmid: 17412618
references.citation: Immunity. 2006 Aug;25(2):309-18
references.pmid: 16919486
references.citation: Immunity. 2006 May;24(5):623-32
references.pmid: 16713979
references.citation: Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8263-7
references.pmid: 8058792
references.citation: J Immunol. 2001 Jun 1;166(11):6972-81
references.pmid: 11359859
references.citation: J Exp Med. 2000 Jul 17;192(2):295-302
references.pmid: 10899916
references.citation: Immunity. 2008 Aug 15;29(2):306-17
references.pmid: 18691912
references.citation: Immunol Cell Biol. 2008 Jul;86(5):398-408
references.pmid: 18392044
references.citation: J Immunol. 2009 Jan 15;182(2):1107-18
references.pmid: 19124754
references.citation: J Immunol. 2006 Nov 1;177(9):5852-60
references.pmid: 17056509
references.citation: J Exp Med. 2007 Aug 6;204(8):1757-64
references.pmid: 17620361
references.citation: Blood. 2009 Apr 9;113(15):3418-27
references.pmid: 19176316
references.citation: J Immunol. 2006 Jan 15;176(2):803-10
references.pmid: 16393963
references.citation: Hepatology. 2008 May;47(5):1557-66
references.pmid: 18318443
references.citation: Nat Immunol. 2006 Mar;7(3):311-7
references.pmid: 16462739
references.citation: Annu Rev Immunol. 2003;21:685-711
references.pmid: 12615891
references.citation: J Immunol. 1998 Apr 15;160(8):4067-73
references.pmid: 9558117
references.citation: Nature. 1994 Nov 10;372(6502):190-3
references.pmid: 7969453
references.citation: Immunity. 2009 Sep 18;31(3):502-12
references.pmid: 19733097
references.citation: Immunity. 2009 Sep 18;31(3):513-25
references.pmid: 19733489
references.citation: Gastroenterology. 2005 Jul;129(1):50-65
references.pmid: 16012934
references.citation: Immunity. 2003 Jul;19(1):71-82
references.pmid: 12871640
references.citation: J Exp Med. 2005 Oct 17;202(8):1051-61
references.pmid: 16216886
references.citation: Immunity. 2000 May;12(5):495-503
references.pmid: 10843382
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: J Exp Med. 1992 Dec 1;176(6):1693-702
references.pmid: 1460426
references.citation: Nature. 2007 Jul 26;448(7152):427-34
references.pmid: 17653185
references.citation: Immunity. 1999 Jan;10(1):39-49
references.pmid: 10023769
references.citation: Nat Immunol. 2004 Nov;5(11):1124-33
references.pmid: 15475957
references.citation: Science. 1991 Mar 22;251(5000):1451-5
references.pmid: 2006419
references.citation: J Exp Med. 2006 Oct 30;203(11):2473-83
references.pmid: 17030949
references.citation: Gastroenterology. 2000 Sep;119(3):715-23
references.pmid: 10982766
references.citation: Immunity. 2007 Oct;27(4):610-24
references.pmid: 17936032
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Immunity. 2008 Apr;28(4):559-70
references.pmid: 18400195
references.citation: Annu Rev Immunol. 2000;18:767-811
references.pmid: 10837075
references.citation: Nat Immunol. 2009 Apr;10(4):394-402
references.pmid: 19252492
references.citation: J Exp Med. 2009 Aug 31;206(9):1995-2011
references.pmid: 19703989
references.citation: Immunity. 2003 Jul;19(1):59-70
references.pmid: 12871639
references.citation: J Exp Med. 2005 Oct 17;202(8):1063-73
references.pmid: 16216890
references.citation: Nature. 1993 Jan 7;361(6407):82-5
references.pmid: 8421498