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Mechanisms in allergic airway inflammation – lessons from studies in the mouse

  • Bennett O.V. Shum (a1) (a2), Michael S. Rolph (a1) (a2) and William A. Sewell (a1) (a3)

Asthma is a chronic inflammatory disease of the airways, involving recurrent episodes of airway obstruction and wheezing. A common pathological feature in asthma is the presence of a characteristic allergic airway inflammatory response involving extensive leukocyte infiltration, mucus overproduction and airway hyper-reactivity. The pathogenesis of allergic airway inflammation is complex, involving multiple cell types such as T helper 2 cells, regulatory T cells, eosinophils, dendritic cells, mast cells, and parenchymal cells of the lung. The cellular response in allergic airway inflammation is controlled by a broad range of bioactive mediators, including IgE, cytokines and chemokines. The asthmatic allergic inflammatory response has been a particular focus of efforts to develop novel therapeutic agents. Animal models are widely used to investigate inflammatory mechanisms. Although these models are not perfect replicas of clinical asthma, such studies have led to the development of numerous novel therapeutic agents, of which some have already been successful in clinical trials.

Corresponding author
*Corresponding author: William Sewell, Immunology and Inflammation Research Program, Garvan Institute for Medical Research, 384 Victoria St, Darlinghurst, New South Wales 2010, Australia. Tel: +61 2 9295 8434; Fax: +61 2 9295 8404; E-mail:
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1M. Masoli (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59, 469-478

3L. von Hertzen and T. Haahtela (2005) Signs of reversing trends in prevalence of asthma. Allergy 60, 283-292

4K.B. Weiss and S.D. Sullivan (2001) The health economics of asthma and rhinitis. I. Assessing the economic impact. J Allergy Clin Immunol 107, 3-8

5J. Mallol (2008) Heightened bronchial hyperresponsiveness in the absence of heightened atopy in children with current wheezing and low income status. Thorax 63, 167-171

6M. Wills-Karp (1999) Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 17, 255-281

7J. Douwes (2002) Non-eosinophilic asthma: importance and possible mechanisms. Thorax 57, 643-648

8G.R. Zosky and P.D. Sly (2007) Animal models of asthma. Clin Exp Allergy 37, 973-988

9C.G. Persson (2002) Con: mice are not a good model of human airway disease. Am J Respir Crit Care Med 166, 6-7; discussion 8

10K. Clark (2004) Eosinophil degranulation in the allergic lung of mice primarily occurs in the airway lumen. J Leukoc Biol 75, 1001-1009

11R.K. Kumar and P.S. Foster (2002) Modeling allergic asthma in mice: pitfalls and opportunities. Am J Respir Cell Mol Biol 27, 267-272

12J.R. Johnson (2004) Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Respir Crit Care Med 169, 378-385

13G.R. Zosky (2008) Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation. Clin Exp Allergy 38, 829-838

14E.W. Gelfand (2002) Pro: mice are a good model of human airway disease. Am J Respir Crit Care Med 166, 5-6; discussion 7-8

15S.H. Gavett (1994) Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol 10, 587-593

16L. Cohn , J.A. Elias and G.L. Chupp (2004) Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22, 789-815

17D.S. Robinson (1992) Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326, 298-304

18A.K. Abbas , K.M. Murphy and A. Sher (1996) Functional diversity of helper T lymphocytes. Nature 383, 787-793

19D. Amsen (2004) Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117, 515-526

20M.H. Kaplan (1996) Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4, 313-319

21M. Kopf (1993) Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362, 245-248

22T. Akimoto (1998) Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice. J Exp Med 187, 1537-1542

23A. Mathew (2001) Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation. J Exp Med 193, 1087-1096

24Y. Gernez (2007) Altered phosphorylated signal transducer and activator of transcription profile of CD4+CD161+ T cells in asthma: modulation by allergic status and oral corticosteroids. J Allergy Clin Immunol 120, 1441-1448

25W. Zheng and R.A. Flavell (1997) The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89, 587-596

26I.C. Ho , D. Lo and L.H. Glimcher (1998) c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and -independent mechanisms. J Exp Med 188, 1859-1866

27J. Rengarajan , B. Tang and L.H. Glimcher (2002) NFATc2 and NFATc3 regulate T(H)2 differentiation and modulate TCR-responsiveness of naive T(H)cells. Nat Immunol 3, 48-54

28M. Rincon and R.A. Flavell (1997) Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells. Mol Cell Biol 17, 1522-1534

29A. Masuda (2004) The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells. J Immunol 173, 5564-5573

30L. Tu (2005) Notch signaling is an important regulator of type 2 immunity. J Exp Med 202, 1037-1042

31D. Amsen (2007) Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 27, 89-99

32M.H. Kaplan (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382, 174-177

33R.A. Seder (1993) Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci U S A 90, 10188-10192

34S.J. Szabo (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669

35T. Usui (2006) T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203, 755-766

36S. Finotto (2002) Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336-338

37F.W. Ko (2007) Decreased T-bet expression and changes in chemokine levels in adults with asthma. Clin Exp Immunol 147, 526-532

38E. Bettelli , T. Korn and V.K. Kuchroo (2007) Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 19, 652-657

39II Ivanov (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133

40E.V. Acosta-Rodriguez (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8, 942-949

41M. Veldhoen (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189

42T. Korn (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448, 484-487

43C.L. Langrish (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201, 233-240

44K. Wing , Z. Fehervari and S. Sakaguchi (2006) Emerging possibilities in the development and function of regulatory T cells. Int Immunol 18, 991-1000

45N. Watanabe (2005) Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436, 1181-1185

46S. Sakaguchi (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22, 531-562

47N. Seddiki (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203, 1693-1700

48J. Kearley (2005) Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 202, 1539-1547

49I.P. Lewkowich (2005) CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med 202, 1549-1561

50Y.C. Su (2006) Cyclophosphamide augments inflammation by reducing immunosuppression in a mouse model of allergic airway disease. J Allergy Clin Immunol 117, 635-641

51O. Akbari , R.H. DeKruyff and D.T. Umetsu (2001) Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2, 725-731

52D.H. Strickland (2006) Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J Exp Med 203, 2649-2660

53E.M. Ling (2004) Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363, 608-615

55T. Kamradt , R. Goggel and K.J. Erb (2005) Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection. Trends Immunol 26, 260-267

56M. Yazdanbakhsh , A. van den Biggelaar and R.M. Maizels (2001) Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol 22, 372-377

57M. Yazdanbakhsh , P.G. Kremsner and R. van Ree (2002) Allergy, parasites, and the hygiene hypothesis. Science 296, 490-494

58M.S. Wilson (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202, 1199-1212

59G. Wohlleben (2004) Helminth infection modulates the development of allergen-induced airway inflammation. Int Immunol 16, 585-596

60P.A. Stumbles (1998) Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity. J Exp Med 188, 2019-2031

61B.N. Lambrecht (2000) Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 106, 551-559

62L.S. van Rijt (2004) Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of TH2 effector responses in a mouse model of asthma. J Allergy Clin Immunol 114, 166-173

63S. Radhakrishnan (2005) Dendritic cells activated by cross-linking B7-DC (PD-L2) block inflammatory airway disease. J Allergy Clin Immunol 116, 668-674

64M.C. Genovese (2005) Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353, 1114-1123

65Y.H. Wang (2006) Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity 24, 827-838

66A. Al-Shami (2004) A role for thymic stromal lymphopoietin in CD4(+) T cell development. J Exp Med 200, 159-168

67A. Al-Shami (2005) A role for TSLP in the development of inflammation in an asthma model. J Exp Med 202, 829-839

68S. Ying (2005) Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol 174, 8183-8190

69M. Rimoldi (2005) Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6, 507-514

70M.E. Rothenberg and S.P. Hogan (2006) The eosinophil. Annu Rev Immunol 24, 147-174

71S.Y. Eum (1995) Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness. Proc Natl Acad Sci U S A 92, 12290-12294

72P.S. Foster (1996) Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 183, 195-201

73D.B. Corry (1996) Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 183, 109-117

74K.G. Tournoy (2000) Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Clin Exp Allergy 30, 79-85

75J.A. Wilder (1999) Dissociation of airway hyperresponsiveness from immunoglobulin E and airway eosinophilia in a murine model of allergic asthma. Am J Respir Cell Mol Biol 20, 1326-1334

76A.A. Humbles (2004) A critical role for eosinophils in allergic airways remodeling. Science 305, 1776-1779

77J.J. Lee (2004) Defining a link with asthma in mice congenitally deficient in eosinophils. Science 305, 1773-1776

78J.S. Marshall and D.M. Jawdat (2004) Mast cells in innate immunity. J Allergy Clin Immunol 114, 21-27

79T. Kawakami and S.J. Galli (2002) Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol 2, 773-786

80A. Lorentz (2000) Human intestinal mast cells are capable of producing different cytokine profiles: role of IgE receptor cross-linking and IL-4. J Immunol 164, 43-48

81P. Bradding (1994) Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 10, 471-480

82P. Bradding , A.F. Walls and S.T. Holgate (2006) The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol 117, 1277-1284

83Y.I. Nigo (2006) Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc Natl Acad Sci U S A 103, 2286-2291

84C.M. Williams and S.J. Galli (2000) Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 192, 455-462

86E.S. Schulman (2001) Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med 164, S6-11

87J.V. Fahy (1997) The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med 155, 1828-1834

88R. Djukanovic (2004) Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med 170, 583-593

89A.C. Wu (2007) Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model. J Allergy Clin Immunol 120, 1146-1152

90D.A. Knight and S.T. Holgate (2003) The airway epithelium: structural and functional properties in health and disease. Respirology 8, 432-446

91A. Komiya (2003) Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells. Cell Immunol 225, 91-100

92C. Hahn (2006) Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation. J Allergy Clin Immunol 117, 787-794

93A. Braun (1998) Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Immunol 28, 3240-3251

94N. Asokananthan (2002) Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. J Immunol 168, 3577-3585

96J.L. Lordan (2002) Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells. J Immunol 169, 407-414

97M. Pichavant (2005) Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment. J Allergy Clin Immunol 115, 771-778

98I. Boldogh (2005) ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 115, 2169-2179

99Z. Hassim , S.E. Maronese and R.K. Kumar (1998) Injury to murine airway epithelial cells by pollen enzymes. Thorax 53, 368-371

100D.H. Broide (2005) Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epithelium. Proc Natl Acad Sci U S A 102, 17723-17728

102T. Madan (2001) Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest 107, 467-475

103B.O. Shum (2006) The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation. J Clin Invest 116, 2183-2192

104C.M. Lloyd (2001) Mouse models of allergic airway disease. Adv Immunol 77, 263-295

105J.D. Moffatt (2005) What targets have knockouts revealed in asthma? Pharmacol Ther 107, 343-357

107G. Le Gros (1990) Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172, 921-929

109A.E. Kelly-Welch (2003) Interleukin-4 and interleukin-13 signaling connections maps. Science 300, 1527-1528

110L. Cohn (1997) Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production. J Exp Med 186, 1737-1747

111G. Brusselle (1995) Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. Am J Respir Cell Mol Biol 12, 254-259

113L.C. Borish (2001) Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 107, 963-970

114C. Walker (1992) Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146, 109-115

115A.K. Johansson (2004) Allergen-induced traffic of bone marrow eosinophils, neutrophils and lymphocytes to airways. Eur J Immunol 34, 3135-3145

116M.J. Leckie (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356, 2144-2148

117P. Flood-Page (2007) A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 176, 1062-1071

118J.C. Kips (2003) Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 167, 1655-1659

119P.T. Flood-Page (2003) Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 167, 199-204

120A. Soussi-Gounni , M. Kontolemos and Q. Hamid (2001) Role of IL-9 in the pathophysiology of allergic diseases. J Allergy Clin Immunol 107, 575-582

121U.A. Temann , P. Ray and R.A. Flavell (2002) Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J Clin Invest 109, 29-39

122V. Steenwinckel (2007) IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells. J Immunol 178, 3244-3251

123G. Cheng (2002) Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model. Am J Respir Crit Care Med 166, 409-416

124T.T. Kung (2001) Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice. Am J Respir Cell Mol Biol 25, 600-605

125S.J. McMillan (2002) The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. J Exp Med 195, 51-57

126T.D. Mueller (2002) Structure, binding, and antagonists in the IL-4/IL-13 receptor system. Biochim Biophys Acta 1592, 237-250

127M. Wills-Karp (1998) Interleukin-13: central mediator of allergic asthma. Science 282, 2258-2261

128M. Wills-Karp (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202, 175-190

130M.S. Wilson (2007) IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest 117, 2941-2951

131S. Wenzel (2007) Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 370, 1422-1431

132S.A. Bryan (2000) Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356, 2149-2153

133S.H. Cho (2005) Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma. Am J Respir Crit Care Med 171, 224-230

134N. Krug (1996) T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 14, 319-326

135T.J. Huang (2001) Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma. J Immunol 166, 207-217

136G. Hansen (1999) Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103, 175-183

137D.A. Randolph (1999) Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J Clin Invest 104, 1021-1029

138E.M. Hessel (1997) Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration. Am J Respir Cell Mol Biol 16, 325-334

139R.K. Kumar (2004) Effects of anticytokine therapy in a mouse model of chronic asthma. Am J Respir Crit Care Med 170, 1043-1048

140D.M. Bullens (2006) IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res 7, 135

141S. Henness (2006) IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM. Am J Physiol Lung Cell Mol Physiol 290, L1283-1290

142M.S. Rahman (2006) IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways. J Immunol 177, 4064-4071

143P.W. Hellings (2003) Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol 28, 42-50

144S. Schnyder-Candrian (2006) Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 203, 2715-2725

145M. Feldmann and R.N. Maini (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19, 163-196

146S. Nakae (2007) TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice. J Allergy Clin Immunol 119, 680-686

147M.A. Berry (2006) Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 354, 697-708

148A. Rot and U.H. von Andrian (2004) Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 22, 891-928

149C. Palmqvist , A.J. Wardlaw and P. Bradding (2007) Chemokines and their receptors as potential targets for the treatment of asthma. Br J Pharmacol 151, 725-736

150J.J. Smit and N.W. Lukacs (2006) A closer look at chemokines and their role in asthmatic responses. Eur J Pharmacol 533, 277-288

151H. Heath (1997) Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J Clin Invest 99, 178-184

152S.M. Pope (2005) The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol 175, 5341-5350

153A.A. Humbles (2002) The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A 99, 1479-1484

154W. Ma (2002) CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest 109, 621-628

155A.M. Das (2006) Selective inhibition of eosinophil influx into the lung by small molecule CCR3 antagonists in mouse models of allergic inflammation. J Pharmacol Exp Ther 318, 411-417

156P. Loetscher (2001) The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3. J Biol Chem 276, 2986-2991

157G. Xanthou (2003) CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11. Eur J Immunol 33, 2241-2250

158P.C. Fulkerson (2004) Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-gamma (Mig, CXCL9). Proc Natl Acad Sci U S A 101, 1987-1992

159M.S. Thomas , S.L. Kunkel and N.W. Lukacs (2002) Differential role of IFN-gamma-inducible protein 10 kDa in a cockroach antigen-induced model of allergic airway hyperreactivity: systemic versus local effects. J Immunol 169, 7045-7053

160B.D. Medoff (2002) IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol 168, 5278-5286

161M. Mellado (2008) Chemokine receptor 2 blockade prevents asthma in a cynomolgus monkey model. J Pharmacol Exp Ther 324, 769-775

162A.J. Morgan (2005) IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR 3 and CCR 4. J Allergy Clin Immunol 116, 594-600

164T. Sekiya (2000) Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells. J Immunol 165, 2205-2213

165S.M. Propst (2000) Proinflammatory and Th2-derived cytokines modulate CD40-mediated expression of inflammatory mediators in airway epithelia: implications for the role of epithelial CD40 in airway inflammation. J Immunol 165, 2214-2221

166M. Weckmann (2007) Critical link between TRAIL and CCL20 for the activation of T(H)2 cells and the expression of allergic airway disease. Nat Med 13, 1308-1315

167T. Sharkhuu (2006) Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity. Clin Exp Allergy 36, 1575-1583

168S. Okumura (2005) FcepsilonRI-mediated amphiregulin production by human mast cells increases mucin gene expression in epithelial cells. J Allergy Clin Immunol 115, 272-279

169D.M. Zaiss (2006) Amphiregulin, a TH2 cytokine enhancing resistance to nematodes. Science 314, 1746

170S.A. Ritz (2002) On the generation of allergic airway diseases: from GM-CSF to Kyoto. Trends Immunol 23, 396-402

171Y.C. Su (2008) Granulocyte-macrophage colony-stimulating factor is required for bronchial eosinophilia in a murine model of allergic airway inflammation. J Immunol 180, 2600-2607

172P.G. Holt (2004) Drug development strategies for asthma: in search of a new paradigm. Nat Immunol 5, 695-698

A.B. Kay (2005) The role of eosinophils in the pathogenesis of asthma. Trends Mol Med 11, 148-152

S.T. Holgate and R. Polosa (2006) The mechanisms, diagnosis, and management of severe asthma in adults. Lancet 368, 780-793

T.B. Casale and J.R. Stokes (2008) Immunomodulators for allergic respiratory disorders. J Allergy Clin Immunol 121, 288-296

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