title: Emerging roles of T helper subsets in the pathogenesis of asthma.
abstract: The cardinal features of asthma include pulmonary inflammation and airway hyperresponsiveness (AHR). Classically, asthma, specifically allergic asthma, has been attributed to a hyperactive Th2 cell immune response. However, the Th2 cell-mediated inflammation model has failed to adequately explain many of the clinical and molecular aspects of asthma. In addition, the outcomes of Th2-targeted therapeutic trials have been disappointing. Thus, asthma is now believed to be a complex and heterogeneous disorder, with several molecular mechanisms underlying the airway inflammation and AHR that is associated with asthma. The original classification of Th1 and Th2 pathways has recently been expanded to include additional effector Th cell subsets. These include Th17, Th9 and Treg cells. Emerging data highlight the involvement of these new Th cell subsets in the initiation and augmentation of airway inflammation and asthmatic responses. We now review the roles of these recently classified effector Th cell subsets in asthmatic inflammation and the insights they may provide in addition to the traditional Th2 paradigm. The hope is that a clearer understanding of the inflammatory pathways involved and the mediators of inflammation will yield better targeted therapeutics.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Durrant
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
references.citation: J Leukoc Biol. 2001 Apr;69(4):538-47
references.pmid: 11310839
references.citation: Am J Respir Crit Care Med. 1994 Oct;150(4):1038-48
references.pmid: 7921434
references.citation: Lancet. 1998 Jul 11;352(9122):113
references.pmid: 9672280
references.citation: Immunity. 2008 Apr;28(4):546-58
references.pmid: 18387831
references.citation: J Immunol. 2009 Oct 15;183(8):5293-300
references.pmid: 19783683
references.citation: Nat Immunol. 2008 Dec;9(12):1341-6
references.pmid: 18931678
references.citation: Laryngoscope. 2003 Oct;113(10):1803-12
references.pmid: 14520110
references.citation: Nature. 2006 May 11;441(7090):235-8
references.pmid: 16648838
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: Allergy. 2004 May;59(5):469-78
references.pmid: 15080825
references.citation: Chem Immunol Allergy. 2006;91:59-75
references.pmid: 16354949
references.citation: J Immunol. 1998 Dec 1;161(11):6383-9
references.pmid: 9834129
references.citation: Curr Opin Pulm Med. 2007 Jan;13(1):19-23
references.pmid: 17133120
references.citation: Lancet. 2000 Dec 23-30;356(9248):2149-53
references.pmid: 11191543
references.citation: J Immunol. 1996 Apr 15;156(8):2680-5
references.pmid: 8609383
references.citation: Am J Respir Crit Care Med. 2005 Feb 1;171(3):224-30
references.pmid: 15502111
references.citation: Arch Pathol Lab Med. 2006 Apr;130(4):447-51
references.pmid: 16594736
references.citation: Clin Exp Allergy. 2009 Sep;39(9):1314-23
references.pmid: 19538496
references.citation: J Allergy Clin Immunol. 2000 Jan;105(1 Pt 1):108-15
references.pmid: 10629460
references.citation: Allergy. 2000 Jun;55(6):531-9
references.pmid: 10858983
references.citation: Mucosal Immunol. 2009 Sep;2(5):383-92
references.pmid: 19587638
references.citation: J Immunol. 2000 Oct 1;165(7):4051-61
references.pmid: 11034416
references.citation: Arthritis Rheum. 2002 Mar;46(3):802-5
references.pmid: 11920418
references.citation: J Clin Invest. 1999 Jan;103(2):175-83
references.pmid: 9916129
references.citation: J Exp Med. 2004 Jun 7;199(11):1567-75
references.pmid: 15173208
references.citation: J Allergy Clin Immunol. 2004 Jun;113(6):1025-34; quiz 1035
references.pmid: 15208578
references.citation: Lancet. 2007 Oct 20;370(9596):1422-31
references.pmid: 17950857
references.citation: J Immunol. 1998 Oct 15;161(8):3813-6
references.pmid: 9780144
references.citation: J Immunol. 1999 Feb 1;162(3):1246-51
references.pmid: 9973376
references.citation: J Exp Med. 1997 Mar 17;185(6):1089-99
references.pmid: 9091582
references.citation: Thorax. 1993 Jan;48(1):26-32
references.pmid: 8434349
references.citation: Am J Respir Cell Mol Biol. 1995 Jul;13(1):54-9
references.pmid: 7598937
references.citation: Clin Exp Immunol. 2001 Aug;125(2):177-83
references.pmid: 11529906
references.citation: Am J Respir Crit Care Med. 1998 Feb;157(2):403-9
references.pmid: 9476850
references.citation: Nat Med. 2006 May;12(5):518-25
references.pmid: 16633347
references.citation: N Engl J Med. 2009 Mar 5;360(10):1002-14
references.pmid: 19264689
references.citation: Am J Respir Crit Care Med. 2008 Nov 15;178(10):1023-32
references.pmid: 18787221
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: J Exp Med. 2005 Dec 5;202(11):1549-61
references.pmid: 16314437
references.citation: J Immunol. 1999 Feb 15;162(4):2347-52
references.pmid: 9973514
references.citation: J Immunol. 2001 Oct 15;167(8):4430-5
references.pmid: 11591768
references.citation: J Exp Med. 2006 Nov 27;203(12):2715-25
references.pmid: 17101734
references.citation: J Gene Med. 2006 Dec;8(12):1393-9
references.pmid: 17019745
references.citation: J Allergy Clin Immunol. 2007 Mar;119(3):662-70
references.pmid: 17336616
references.citation: Am J Respir Cell Mol Biol. 1998 Nov;19(5):713-20
references.pmid: 9806735
references.citation: N Engl J Med. 1989 Feb 2;320(5):271-7
references.pmid: 2911321
references.citation: Thorax. 2007 Mar;62(3):211-8
references.pmid: 16844729
references.citation: Thorax. 2002 Oct;57(10):875-9
references.pmid: 12324674
references.citation: Am J Respir Crit Care Med. 1998 Jan;157(1):256-62
references.pmid: 9445307
references.citation: Respirology. 2006 Jan;11(1):54-61
references.pmid: 16423202
references.citation: BMC Public Health. 2009 Jun 29;9:210
references.pmid: 19563637
references.citation: Lancet. 2000 Dec 23-30;356(9248):2144-8
references.pmid: 11191542
references.citation: Immunity. 2002 Sep;17(3):375-87
references.pmid: 12354389
references.citation: Am J Respir Crit Care Med. 2006 Jan 1;173(1):64-70
references.pmid: 16179640
references.citation: Nature. 2006 Aug 31;442(7106):997-1002
references.pmid: 16921386
references.citation: J Allergy Clin Immunol. 1998 Jul;102(1):86-93
references.pmid: 9679851
references.citation: J Immunol. 2008 Apr 15;180(8):5625-35
references.pmid: 18390747
references.citation: Int Arch Allergy Immunol. 2005;137 Suppl 1:51-4
references.pmid: 15947485
references.citation: J Allergy Clin Immunol. 2003 Mar;111(3):450-63; quiz 464
references.pmid: 12642820
references.citation: Immunol Rev. 2008 Jun;223:114-31
references.pmid: 18613832
references.citation: Chest. 2003 Mar;123(3 Suppl):370S
references.pmid: 12628982
references.citation: Nat Immunol. 2008 Dec;9(12):1347-55
references.pmid: 18997793
references.citation: J Exp Med. 1997 Aug 4;186(3):343-7
references.pmid: 9265074
references.citation: J Immunol. 1997 Apr 1;158(7):3539-44
references.pmid: 9120316
references.citation: J Clin Invest. 1999 Nov;104(10):1375-82
references.pmid: 10562299
references.citation: J Allergy Clin Immunol. 2008 Jan;121(1):51-6
references.pmid: 17949803
references.citation: Allergy. 2000 Apr;55(4):355-62
references.pmid: 10782520
references.citation: Nature. 2003 Feb 13;421(6924):744-8
references.pmid: 12610626
references.citation: Nat Med. 2007 Feb;13(2):139-45
references.pmid: 17290272
references.citation: Am J Respir Cell Mol Biol. 2003 Jan;28(1):9-11
references.pmid: 12495927
references.citation: J Exp Med. 2003 Dec 15;198(12):1951-7
references.pmid: 14662908
references.citation: Nat Immunol. 2008 Jun;9(6):641-9
references.pmid: 18454151
references.citation: J Allergy Clin Immunol. 2008 Sep;122(3):617-24.e6
references.pmid: 18672278
references.citation: J Biol Chem. 2003 Jan 17;278(3):1910-4
references.pmid: 12417590
references.citation: Nature. 1996 Oct 31;383(6603):787-93
references.pmid: 8893001
references.citation: J Allergy Clin Immunol. 2009 May;123(5):1004-11
references.pmid: 19410689
references.citation: J Allergy Clin Immunol. 2004 Mar;113(3):462-9
references.pmid: 15007348
references.citation: Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407-13
references.pmid: 2252260
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: Clin Exp Allergy. 2006 Dec;36(12):1575-83
references.pmid: 17177681
references.citation: J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2
references.pmid: 8939179
references.citation: Immunity. 2009 Sep 18;31(3):425-37
references.pmid: 19766085
references.citation: Chest. 2007 Sep;132(3):1007-14
references.pmid: 17873195
references.citation: Immunology. 2009 Aug;127(4):450-8
references.pmid: 19604299
references.citation: Int Immunol. 2006 Jul;18(7):991-1000
references.pmid: 16720616
references.citation: Allergol Int. 2008 Jun;57(2):121-34
references.pmid: 18427165
references.citation: Annu Rev Immunol. 2004;22:789-815
references.pmid: 15032597
references.citation: Annu Rev Immunol. 1999;17:255-81
references.pmid: 10358759
references.citation: Thorax. 2002 Jul;57(7):643-8
references.pmid: 12096210
references.citation: J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):133-5
references.pmid: 7822655
references.citation: J Immunol. 2006 Sep 15;177(6):4064-71
references.pmid: 16951370
references.citation: J Biol Chem. 2003 May 9;278(19):17036-43
references.pmid: 12624114
references.citation: Lancet. 2008 Sep 20;372(9643):1107-19
references.pmid: 18805339
references.citation: J Allergy Clin Immunol. 2003 Jun;111(6):1319-27
references.pmid: 12789235
references.citation: Clin Exp Allergy. 2008 Jun;38(6):872-97
references.pmid: 18498538
references.citation: Am J Respir Cell Mol Biol. 1994 Jun;10(6):587-93
references.pmid: 8003337
references.citation: Am J Respir Crit Care Med. 2002 Aug 1;166(3):409-16
references.pmid: 12153980
references.citation: J Immunol. 2000 Dec 1;165(11):6107-15
references.pmid: 11086043
references.citation: Clin Exp Allergy. 2002 Jun;32(6):866-71
references.pmid: 12047433
references.citation: J Exp Med. 2002 Jan 7;195(1):51-7
references.pmid: 11781365
references.citation: J Allergy Clin Immunol. 2005 May;115(5):973-81
references.pmid: 15867854
references.citation: J Allergy Clin Immunol. 2001 Nov;108(5):804-9
references.pmid: 11692108
references.citation: Trends Pharmacol Sci. 1994 Sep;15(9):324-32
references.pmid: 7992386
references.citation: Respir Med. 2003 Jun;97(6):726-33
references.pmid: 12814161
references.citation: Ciba Found Symp. 1997;206:56-67; discussion 67-70, 106-10
references.pmid: 9257005
references.citation: Am J Respir Crit Care Med. 2005 Jan 1;171(1):12-8
references.pmid: 15477493
references.citation: J Allergy Clin Immunol. 2007 Jul;120(1):48-55
references.pmid: 17482668
references.citation: J Allergy Clin Immunol. 2001 Sep;108(3):430-8
references.pmid: 11544464
references.citation: Immunity. 2009 May;30(5):646-55
references.pmid: 19464987
references.citation: Science. 2002 Jan 11;295(5553):336-8
references.pmid: 11786643
references.citation: Nat Immunol. 2002 Aug;3(8):715-20
references.pmid: 12145657
references.citation: Chest. 1997 Aug;112(2):523-9
references.pmid: 9266893
references.citation: J Exp Med. 1997 Nov 17;186(10):1737-47
references.pmid: 9362533
references.citation: J Allergy Clin Immunol. 2001 Mar;107(3):499-504
references.pmid: 11240951
references.citation: Am J Respir Crit Care Med. 1996 Nov;154(5):1257-60
references.pmid: 8912732
references.citation: J Exp Med. 2005 Dec 5;202(11):1539-47
references.pmid: 16314435
references.citation: J Allergy Clin Immunol. 2003 Jun;111(6):1293-8
references.pmid: 12789232
references.citation: Respir Res. 2006 Nov 03;7:135
references.pmid: 17083726
references.citation: J Allergy Clin Immunol. 1997 Feb;99(2):S781-6
references.pmid: 9042071
references.citation: Am J Respir Crit Care Med. 1999 Sep;160(3):1001-8
references.pmid: 10471631
references.citation: Immunol Rev. 1988 Feb;102:5-28
references.pmid: 2966762
references.citation: J Exp Med. 1998 Oct 5;188(7):1307-20
references.pmid: 9763610
references.citation: Nat Rev Immunol. 2008 Mar;8(3):218-30
references.pmid: 18274559
references.citation: Am J Respir Crit Care Med. 1996 Feb;153(2):535-9
references.pmid: 8564093
references.citation: Nature. 2008 Jun 19;453(7198):1051-7
references.pmid: 18563156
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15817-22
references.pmid: 17893340
references.citation: Am Rev Respir Dis. 1993 Feb;147(2):291-5
references.pmid: 8430950
references.citation: J Immunol. 2003 Dec 1;171(11):6173-7
references.pmid: 14634133
references.citation: Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):970-7
references.pmid: 1970229
references.citation: Eur Respir J. 2002 Mar;19(3):534-7
references.pmid: 11936535
references.citation: Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 2):S215-7
references.pmid: 10712378
references.citation: Am J Respir Cell Mol Biol. 2003 Jan;28(1):42-50
references.pmid: 12495931
references.citation: N Engl J Med. 1992 Jan 30;326(5):298-304
references.pmid: 1530827
references.citation: Nat Immunol. 2005 Nov;6(11):1123-32
references.pmid: 16200070
references.citation: Cell. 2006 Sep 22;126(6):1121-33
references.pmid: 16990136