title: Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4.
abstract: T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC-activated T cells traffic more efficiently into the lung in response to inhaled antigen and at homeostasis compared with T cells activated by DCs from other tissues. Consequently, lung DC-imprinted T cells protect against influenza more effectively than do gut and skin DC-imprinted T cells. Lung DCs imprint the expression of CCR4 on T cells, and CCR4 contributes to T cell lung imprinting. Lung DC-activated, CCR4-deficient T cells fail to traffic into the lung as efficiently and to protect against influenza as effectively as lung DC-activated, CCR4-sufficient T cells. Thus, lung DCs imprint T cell lung homing and promote lung immunity in part through CCR4.
authors: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Zamaneh
authors: Z
authors: Mikhak
authors: James P
authors: JP
authors: Strassner
authors: Andrew D
authors: AD
authors: Luster
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D054398:Receptors, CCR4 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000941:Antigens; C515355:Ccr4 protein, mouse; D054398:Receptors, CCR4
references: Science. 2001 Mar 23;291(5512):2413-7
references: 11264538
references: J Immunol. 2004 Jan 15;172(2):857-63
references: 14707056
references: Cancer Res. 2009 Jul 15;69(14):5996-6004
references: 19567680
references: J Exp Med. 2008 Nov 24;205(12):2839-50
references: 18981237
references: J Immunol. 2012 Sep 15;189(6):2879-89
references: 22875804
references: J Allergy Clin Immunol. 2013 Jun;131(6):1644-52
references: 23632297
references: J Immunol. 2013 Jan 1;190(1):296-306
references: 23197262
references: Methods Mol Biol. 2010;595:231-3
references: 19941116
references: J Exp Med. 2005 Jan 17;201(2):303-16
references: 15642741
references: J Exp Med. 2000 Jan 17;191(2):265-74
references: 10637271
references: J Immunol. 2004 Apr 15;172(8):4875-82
references: 15067066
references: J Immunol. 2001 Feb 1;166(3):2055-62
references: 11160256
references: Blood. 2003 Mar 1;101(5):1677-82
references: 12406880
references: J Immunol. 2004 Feb 1;172(3):1575-81
references: 14734737
references: J Infect Dis. 2011 Sep 15;204(6):845-53
references: 21846636
references: J Immunol. 2006 Apr 15;176(8):4959-67
references: 16585592
references: J Exp Med. 2003 Sep 15;198(6):963-9
references: 12963696
references: J Immunol. 2011 Dec 1;187(11):5510-4
references: 22058417
references: J Exp Med. 2009 Feb 16;206(2):359-70
references: 19153243
references: Nat Med. 2010 May;16(5):558-64, 1p following 564
references: 20436484
references: MMWR Morb Mortal Wkly Rep. 2013 Feb 22;62(7):119-23
references: 23425960
references: PLoS One. 2011 Apr 29;6(4):e19346
references: 21559409
references: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10598-603
references: 16027362
references: Am J Pathol. 2011 Jan;178(1):233-44
references: 21224060
references: Curr Opin Immunol. 2006 Jun;18(3):271-7
references: 16617008
references: Annu Rev Immunol. 2012;30:243-70
references: 22224777
references: Gastroenterology. 2009 Sep;137(3):1006-18, 1018.e1-3
references: 19501588
references: J Exp Med. 2007 Jun 11;204(6):1335-47
references: 17548521
references: Immunity. 2004 Oct;21(4):527-38
references: 15485630
references: J Exp Med. 2000 Nov 20;192(10):1425-40
references: 11085745
references: J Exp Med. 2010 Mar 15;207(3):553-64
references: 20156972
references: J Exp Med. 2002 Jan 7;195(1):135-41
references: 11781372
references: Clin Exp Allergy. 2005 Jan;35(1):26-33
references: 15649262
references: J Clin Invest. 2011 Jun;121(6):2210-20
references: 21537081
references: J Immunol. 2007 Aug 1;179(3):1901-12
references: 17641057
references: Cancer Res. 2000 Jun 15;60(12):3239-46
references: 10866317
references: J Immunol. 2006 Apr 1;176(7):4431-9
references: 16547281
references: Nature. 1999 Aug 19;400(6746):776-80
references: 10466728
references: Lancet Infect Dis. 2012 Jan;12(1):36-44
references: 22032844
references: J Allergy Clin Immunol. 2006 Jan;117(1):204-11
references: 16387607
references: PLoS One. 2011 Jan 26;6(1):e16245
references: 21298112
references: Nature. 2003 Jul 3;424(6944):88-93
references: 12840763
references: J Clin Invest. 2002 Aug;110(4):537-48
references: 12189248
references: Blood. 2012 Nov 29;120(23):4591-8
references: 23043070
references: J Immunol. 2007 Mar 15;178(6):3358-62
references: 17339428
references: J Immunol. 2006 Sep 15;177(6):4149-58
references: 16951380
references: Immunity. 2006 Sep;25(3):511-20
references: 16973385
references: Am J Respir Crit Care Med. 2007 Nov 1;176(9):892-901
references: 17690334
references: J Exp Med. 2000 May 15;191(10):1755-64
references: 10811868
references: J Virol. 2008 May;82(10):4908-19
references: 18353940
references: J Allergy Clin Immunol. 2009 Jan;123(1):67-73.e3
references: 19062085
references: J Exp Med. 2001 Nov 19;194(10):1541-7
references: 11714760
references: J Immunol. 2012 Jun 15;188(12):6347-56
references: 22593615
references: Nature. 2012 Feb 29;483(7388):227-31
references: 22388819
references: J Exp Med. 2001 Jan 1;193(1):51-60
references: 11136820
references: Nat Med. 2010 Feb;16(2):224-7
references: 20081864
references: Eur J Immunol. 2002 May;32(5):1445-54
references: 11981833
references: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2764-9
references: 16473934
references: Nat Immunol. 2007 Mar;8(3):285-93
references: 17259988
references: J Clin Invest. 1997 Sep 1;100(5):1204-8
references: 9276738
references: Am J Pathol. 2002 Jan;160(1):347-55
references: 11786428