A complex role for complement in allergic asthma.
Allergic asthma is a chronic inflammatory disease of the upper airway. It is well appreciated that maladaptive Th2 immunity promotes the allergic phenotype, the underlying mechanisms of which remain elusive. The disease is associated with activation of complement, an ancient danger-sensing component of the innate immune system. Different models of experimental allergic asthma suggest that the small complement fragments of C3 and C5, the anaphylatoxins C3a and C5a, not only promote proallergic effector functions during the allergic effector phase but regulate the development of Th2 immunity during allergen sensitization. The available data support a concept in which C5a is dominant during allergen sensitization and protects against the development of maladaptive Th2 immunity. By contrast, C3a and C5a appear to act synergistically and drive allergic inflammation during the effector phase. In this article, we will review the recent findings in the field to judge the benefit of complement targeting in allergic asthma.
Zhang
Xun
X
Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, OH 45229, USA.
Köhl
Jörg
J
D000818:Animals; D001249:Asthma / Q000276:immunology*; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology
D003165:Complement System Proteins
J Allergy Clin Immunol. 1987 Jul;80(1):24-32
3496373
Mol Immunol. 2009 Sep;46(14):2753-66
19477527
J Immunol. 2003 Mar 15;170(6):3306-14
12626590
Am J Respir Cell Mol Biol. 2004 Aug;31(2):216-9
15039137
Nat Rev Genet. 2004 May;5(5):376-87
15143320
Am J Respir Crit Care Med. 2000 Dec;162(6):2188-93
11112136
Nat Immunol. 2002 Aug;3(8):715-20
12145657
PLoS One. 2008;3(12):e3879
19060952
Clin Exp Allergy. 2007 Sep;37(9):1334-9
17845414
Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1351-8
2252253
J Immunol. 2005 Jan 15;174(2):783-9
15634899
Genes Immun. 2006 Jan;7(1):27-35
16355111
J Exp Med. 2004 Jul 5;200(1):89-98
15238608
J Immunol. 2000 Aug 15;165(4):2183-9
10925305
Mol Immunol. 2007 Jan;44(1-3):57-63
16870256
Immunol Res. 2006;34(2):157-76
16760575
Mol Immunol. 2004 Jun;41(2-3):123-31
15159057
Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 2):S117-22
9351591
Am J Respir Crit Care Med. 2004 Mar 15;169(6):726-32
14701711
Curr Allergy Asthma Rep. 2005 Sep;5(5):362-9
16091207
Annu Rev Immunol. 2008;26:677-704
18173375
Clin Immunol. 2004 Feb;110(2):172-80
15003814
J Immunol. 1998 Jan 15;160(2):1036-43
9551945
Pediatr Allergy Immunol. 2006 Nov;17(7):501-7
17014624
Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1073-8
9563721
J Exp Med. 2005 Dec 5;202(11):1549-61
16314437
Thorax. 1979 Jun;34(3):332-7
483206
J Clin Invest. 2006 Mar;116(3):783-96
16511606
Blood. 2008 Dec 15;112(13):5084-94
18812470
Respir Res. 2006 Oct 17;7:129
17044927
Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1841-3
11734433
Blood. 2008 Feb 15;111(4):2452-61
18056835
J Immunol. 1999 Jun 15;162(12):7409-16
10358194
Hum Mol Genet. 1998 Sep;7(9):1393-8
9700192
J Immunol. 2004 Feb 15;172(4):2530-41
14764726
Immunol Rev. 2004 Dec;202:175-90
15546393
J Immunol. 2001 May 15;166(10):6341-8
11342658
J Immunol. 2001 Oct 15;167(8):4141-5
11591733
Nat Rev Immunol. 2008 Mar;8(3):193-204
18301423
J Exp Med. 2005 Mar 21;201(6):981-91
15781587
Annu Rev Immunol. 2005;23:821-52
15771587
Annu Rev Immunol. 1999;17:255-81
10358759
Int Arch Allergy Appl Immunol. 1991;96(4):305-10
1809688
J Immunol. 2009 Sep 15;183(6):4039-46
19684087
Nat Genet. 1997 Apr;15(4):389-92
9090385
Nature. 2000 Aug 31;406(6799):998-1001
10984054
Curr Opin Mol Ther. 2006 Dec;8(6):529-38
17243489
J Immunol. 2009 Apr 15;182(8):5123-30
19342693
Am J Respir Crit Care Med. 2006 Apr 15;173(8):852-7
16439722
Am J Respir Cell Mol Biol. 2002 Oct;27(4):413-8
12356574
Mol Immunol. 2008 Oct;45(16):4048-56
18692243
J Allergy Clin Immunol. 1997 Aug;100(2):253-60
9275149
Biol Pharm Bull. 1998 Feb;21(2):129-32
9514606
Immunol Lett. 2005 Sep 15;100(2):139-45
16154494
J Allergy Clin Immunol. 2009 Feb;123(2):342-51
19121857
J Immunol. 2002 Nov 15;169(10):5926-33
12421977
J Immunol. 2001 Oct 15;167(8):4651-60
11591795
J Virol. 2007 Jan;81(2):991-9
17079327
J Clin Invest. 2005 Jun;115(6):1590-600
15902311
Am J Respir Crit Care Med. 2003 Dec 1;168(11):1333-41
14500265
Mol Immunol. 2007 Jan;44(1-3):44-56
16889830
Hum Genet. 2004 Sep;115(4):295-301
15278436
J Clin Invest. 2004 Aug;114(3):399-407
15286806
Nat Biotechnol. 2007 Nov;25(11):1265-75
17989689
J Immunol. 2000 Nov 15;165(10):5401-5
11067890
Microbiol Immunol. 2005;49(11):981-6
16301808
Am J Physiol. 1991 Apr;260(4 Pt 1):L254-9
1902064
Mol Immunol. 2006 Jan;43(1-2):13-21
16019071