title: MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion.
abstract: Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Oliphant
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: You Yi
authors.initials: YY
authors.lastname: Hwang
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Walker
authors.affiliation: MRC Human Immunology Unit, NIHR Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, OX3 9DS, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Salimi
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: See Heng
authors.initials: SH
authors.lastname: Wong
authors.affiliation: Institute of Infection, Immunity and Inflammation, GRBC, University Place, Glasgow, G12 8TA, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Englezakis
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Barlow
authors.affiliation: Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Scanlon
authors.affiliation: MRC Human Immunology Unit, NIHR Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, OX3 9DS, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
authors.affiliation: Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland; Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address: anm@mrc-lmb.cam.ac.uk.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D007376:Interleukin-2
references.citation: Clin Exp Immunol. 1995 Oct;102(1):71-7
references.pmid: 7554403
references.citation: Immunity. 2003 Jun;18(6):751-62
references.pmid: 12818157
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15056-61
references.pmid: 10611337
references.citation: Nature. 2010 Jan 28;463(7280):540-4
references.pmid: 20023630
references.citation: Nat Immunol. 2009 Jul;10(7):713-20
references.pmid: 19465907
references.citation: Immunol Cell Biol. 2010 Mar-Apr;88(3):240-3
references.pmid: 20010912
references.citation: Nat Immunol. 2009 Jul;10(7):697-705
references.pmid: 19465906
references.citation: J Immunol. 2012 Feb 1;188(3):1503-13
references.pmid: 22198948
references.citation: J Exp Med. 2013 Dec 16;210(13):2951-65
references.pmid: 24249111
references.citation: Nat Immunol. 2011 May 29;12(7):631-8
references.pmid: 21623379
references.citation: Nature. 2010 Apr 29;464(7293):1367-70
references.pmid: 20200518
references.citation: Nat Med. 2006 Feb;12(2):207-13
references.pmid: 16444266
references.citation: J Exp Med. 2009 Aug 3;206(8):1673-80
references.pmid: 19635864
references.citation: J Exp Med. 2013 Dec 16;210(13):2939-50
references.pmid: 24323357
references.citation: Cell. 1991 Sep 6;66(5):1051-66
references.pmid: 1909605
references.citation: Immunol Cell Biol. 1998 Feb;76(1):34-40
references.pmid: 9553774
references.citation: J Exp Med. 2006 Apr 17;203(4):1105-16
references.pmid: 16606668
references.citation: Immunity. 2003 Nov;19(5):739-48
references.pmid: 14614860
references.citation: Nat Immunol. 2011 Sep 11;12(11):1055-62
references.pmid: 21909091
references.citation: Immunity. 2001 Jan;14(1):1-11
references.pmid: 11163225
references.citation: Immunity. 2010 Sep 24;33(3):364-74
references.pmid: 20817571
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3880-5
references.pmid: 15004274
references.citation: J Exp Med. 2010 Sep 27;207(10):2089-96
references.pmid: 20819926
references.citation: J Exp Med. 2014 Feb 10;211(2):199-208
references.pmid: 24419270
references.citation: Nature. 2013 Jun 6;498(7452):113-7
references.pmid: 23698371
references.citation: J Immunol. 2005 Jan 1;174(1):80-9
references.pmid: 15611230
references.citation: Nature. 1993 Mar 18;362(6417):245-8
references.pmid: 8384701
references.citation: Nat Immunol. 2011 Nov;12(11):1045-54
references.pmid: 21946417
references.citation: Immunity. 2012 Mar 23;36(3):451-63
references.pmid: 22425247
references.citation: Immunity. 2007 Apr;26(4):491-502
references.pmid: 17379546
references.citation: J Exp Med. 2010 Sep 27;207(10):2097-111
references.pmid: 20819925
references.citation: J Exp Med. 2006 Jun 12;203(6):1435-46
references.pmid: 16702603
references.citation: Nat Immunol. 2009 Jul;10(7):706-12
references.pmid: 19465908
references.citation: Immunity. 2010 Mar 26;32(3):426-36
references.pmid: 20303297
references.citation: J Exp Med. 1994 Jan 1;179(1):299-304
references.pmid: 8270872
references.citation: Immunity. 2012 Oct 19;37(4):634-48
references.pmid: 23063333
references.citation: Nat Immunol. 2011 Dec 04;13(1):58-66
references.pmid: 22138715
references.citation: Nat Immunol. 2012 Jan 22;13(3):229-36
references.pmid: 22267218
references.citation: J Exp Med. 1999 Dec 20;190(12):1897-902
references.pmid: 10601364
references.citation: J Exp Med. 2005 Sep 19;202(6):793-804
references.pmid: 16172258
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12423-8
references.pmid: 18719110
references.citation: J Allergy Clin Immunol. 2012 Jan;129(1):191-8.e1-4
references.pmid: 22079492
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11489-94
references.pmid: 20534524
references.citation: Nat Med. 2006 Feb;12(2):214-9
references.pmid: 16444265
references.citation: Immunity. 2002 Jul;17(1):7-17
references.pmid: 12150887
references.citation: J Immunol. 2014 Mar 1;192(5):2442-8
references.pmid: 24470502
references.citation: J Immunol. 2008 Jun 15;180(12):8083-92
references.pmid: 18523272
references.citation: Immunity. 2014 Mar 20;40(3):425-35
references.pmid: 24613091
references.citation: J Immunol. 1991 Aug 1;147(3):781-7
references.pmid: 1861074