title: CD101 inhibits the expansion of colitogenic T cells.
abstract: CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/β independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schey
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Dornhoff
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: J L C
authors.initials: JL
authors.lastname: Baier
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Purtak
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: R
authors.initials: R
authors.lastname: Opoka
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Koller
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Atreya
authors.affiliation: Pathologisches Institut, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: T T
authors.initials: TT
authors.lastname: Rau
authors.affiliation: Nephropathologische Abteilung, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Nephropathologische Abteilung, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Amann
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bogdan
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.|Division of Immunobiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mattner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012720:Severity of Illness Index; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
chemical_list: D015703:Antigens, CD; C093213:CD101 antigen, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D020381:Interleukin-17; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D008562:Membrane Glycoproteins; D016753:Interleukin-10
references.citation: Nat Protoc. 2006;1(6):2900-4
references.pmid: 17406549
references.citation: Nature. 2007 Apr 5;446(7136):685-9
references.pmid: 17377532
references.citation: J Exp Med. 1991 Dec 1;174(6):1549-55
references.pmid: 1744584
references.citation: Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G135-46
references.pmid: 19033538
references.citation: J Exp Med. 2009 Mar 16;206(3):535-48
references.pmid: 19273625
references.citation: Nature. 2012 Nov 22;491(7425):554-9
references.pmid: 23135404
references.citation: Nat Immunol. 2007 Apr;8(4):359-68
references.pmid: 17273171
references.citation: Cell. 1993 Oct 22;75(2):263-74
references.pmid: 8402911
references.citation: Nat Immunol. 2011 Mar;12(3):247-54
references.pmid: 21278738
references.citation: J Immunol. 2008 Jul 1;181(1):721-35
references.pmid: 18566439
references.citation: Immunity. 1994 Oct;1(7):553-62
references.pmid: 7600284
references.citation: Eur J Immunol. 2000 Nov;30(11):3132-9
references.pmid: 11093127
references.citation: J Immunol. 1995 May 1;154(9):4423-33
references.pmid: 7722299
references.citation: Trends Immunol. 2011 Jan;32(1):26-33
references.pmid: 21106439
references.citation: Immunol Rev. 2011 May;241(1):63-76
references.pmid: 21488890
references.citation: Annu Rev Immunol. 2012;30:39-68
references.pmid: 22136167
references.citation: Annu Rev Immunol. 2001;19:683-765
references.pmid: 11244051
references.citation: Cell. 2010 Mar 19;140(6):845-58
references.pmid: 20303875
references.citation: Nat Rev Immunol. 2002 Apr;2(4):251-62
references.pmid: 12001996
references.citation: J Immunol. 2007 Sep 1;179(5):2808-14
references.pmid: 17709494
references.citation: J Immunol. 1995 May 1;154(9):4434-43
references.pmid: 7722300
references.citation: J Exp Med. 2013 Nov 18;210(12):2707-20
references.pmid: 24249704
references.citation: N Engl J Med. 2011 Nov 3;365(18):1713-25
references.pmid: 22047562
references.citation: Mucosal Immunol. 2013 May;6(3):601-11
references.pmid: 23149660
references.citation: Annu Rev Immunol. 2008;26:453-79
references.pmid: 18062768
references.citation: Immunity. 1995 Oct;3(4):521-30
references.pmid: 7584142
references.citation: Nat Immunol. 2012 Jul 01;13(8):770-7
references.pmid: 22751139
references.citation: J Immunol. 1998 Jul 1;161(1):209-17
references.pmid: 9647226
references.citation: Nat Immunol. 2005 Nov;6(11):1142-51
references.pmid: 16227984
references.citation: Immunity. 2011 Apr 22;34(4):554-65
references.pmid: 21511184
references.citation: Aging (Albany NY). 2011 Mar;3(3):192-222
references.pmid: 21422497
references.citation: Nat Immunol. 2002 Jan;3(1):33-41
references.pmid: 11740498
references.citation: J Immunol. 2011 Jul 1;187(1):337-49
references.pmid: 21613619
references.citation: J Immunol. 2009 Aug 15;183(4):2312-20
references.pmid: 19620304
references.citation: Nat Rev Immunol. 2002 Jun;2(6):389-400
references.pmid: 12093005
references.citation: Immunol Rev. 2009 May;229(1):41-66
references.pmid: 19426214
references.citation: Annu Rev Immunol. 2009;27:313-38
references.pmid: 19302043
references.citation: Cell. 1999 Mar 19;96(6):857-68
references.pmid: 10102273
references.citation: N Engl J Med. 2009 Nov 19;361(21):2033-45
references.pmid: 19890111
references.citation: Cell. 2006 Jul 28;126(2):375-87
references.pmid: 16873067
references.citation: Ann N Y Acad Sci. 2013 Mar;1280:30-4
references.pmid: 23551100
references.citation: Nat Rev Immunol. 2009 Sep;9(9):630-44
references.pmid: 19696767
references.citation: Eur J Immunol. 2013 Jul;43(7):1716-26
references.pmid: 23620016
references.citation: Nat Immunol. 2009 Nov;10(11):1178-84
references.pmid: 19783988
references.citation: Gastroenterology. 2009 Jan;136(1):257-67
references.pmid: 18992745
references.citation: J Immunol. 2011 Jul 1;187(1):325-36
references.pmid: 21613616
references.citation: J Immunol. 1996 Oct 15;157(8):3366-74
references.pmid: 8871633
references.citation: N Engl J Med. 2009 Nov 19;361(21):2066-78
references.pmid: 19923578
references.citation: Mol Cell Biol. 2005 Oct;25(20):9115-26
references.pmid: 16199887
references.citation: Immunol Lett. 2007 Nov 30;114(1):1-8
references.pmid: 17936914