Targeting Chemokine Receptors in Allergy

  • Cory M. Hogaboam
Part of the Allergy Frontiers book series (ALLERGY, volume 6)


Allergic and asthmatic diseases stubbornly plague a growing number of Americans and the clinical cost of treating these diseases shows no sign of abating. Persistent peribronchial inflammation (consisting primarily of eosinophils and mononuclear cells) and airway hyperresponsiveness to various stimuli (either antigen-specific or nonspecific) are key features of asthma. Despite concerted efforts in this regard, the mechanisms that lead to the initiation and chronicity of allergic airway inflammation during asthma remain poorly understood. Consequently, the development of inflammation-specific therapeutic interventions for this disorder have proved challenging, but necessary, in light of the fact that the anti-inflammatory effects of corticosteroids diminish with continual use and may not eliminate the airway remodeling features associated with asthma. Recent clinical and basic research suggests that targeting chemokines and/or chemokine receptors shows promise in the treatment of asthma and asthma-like diseases.


Chemokine Receptor Allergy Clin Immunol Invasive Aspergillosis Airway Hyperresponsiveness Airway Remodel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
  2. 2.
    Schaub, B., Lauener, R., and von Mutius, E. 2006. The many faces of the hygiene hypothesis. J Allergy Clin Immunol 117:969–977; quiz 978CrossRefPubMedGoogle Scholar
  3. 3.
    Yazdanbakhsh, M., Kremsner, P.G., and van Ree, R. 2002. Allergy, parasites, and the hygiene hypothesis. Science 296:490–494CrossRefPubMedGoogle Scholar
  4. 4.
    Lugauskas, A., Krikstaponis, A., and Sveistyte, L. 2004. Airborne fungi in industrial environ-ments--potential agents of respiratory diseases. Ann Agric Environ Med 11:19–25PubMedGoogle Scholar
  5. 5.
    Green, B.J., Mitakakis, T.Z., and Tovey, E.R. 2003. Allergen detection from 11 fungal species before and after germination. J Allergy Clin Immunol 111:285–289CrossRefPubMedGoogle Scholar
  6. 6.
    Kauffman, H.F., and van der Heide, S. 2003. Exposure, sensitization, and mechanisms of fungus-induced asthma. Curr Allergy Asthma Rep 3:430–437CrossRefPubMedGoogle Scholar
  7. 7.
    Engelhart, S., et al. 2003. Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. J Hosp Infect 54:300–304CrossRefPubMedGoogle Scholar
  8. 8.
    Schwartz, H.J., and Greenberger, P.A. 1991. The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk. J Lab Clin Med 117:138–142PubMedGoogle Scholar
  9. 9.
    Boulet, L.P., et al. 1997. Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma. Clin Exp Allergy 27:52–59CrossRefPubMedGoogle Scholar
  10. 10.
    Mari, A., et al. 2003. Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts. Clin Exp Allergy 33:1429–1438CrossRefPubMedGoogle Scholar
  11. 11.
    Black, P.N., Udy, A.A., and Brodie, S.M. 2000. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 55:501–504CrossRefPubMedGoogle Scholar
  12. 12.
    Nelson, H.S., et al. 1999. The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program. J Allergy Clin Immunol 104:775–785CrossRefPubMedGoogle Scholar
  13. 13.
    Schuh, J.M., Blease, K., Kunkel, S.L., and Hogaboam, C.M. 2003. Chemokines and cytokines: axis and allies in asthma and allergy. Cytokine Growth Factor Rev 14:503–510CrossRefPubMedGoogle Scholar
  14. 14.
    Randolph, D.A., et al. 1999. The role of CCR7 in TH1 and TH2 cell localization and delivery of B cell help in vivo. Science 286:2159–2162CrossRefPubMedGoogle Scholar
  15. 15.
    Cosmi, L., et al. 2001. Chemoattractant receptors expressed on type 2 t cells and their role in disease. Int Arch Allergy Immunol 125:273–279CrossRefPubMedGoogle Scholar
  16. 16.
    Kallinich, T., et al. 2005. Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients. Clin Exp Allergy 35:26–33CrossRefPubMedGoogle Scholar
  17. 17.
    Ochi, H., et al. 1999. T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J Exp Med 190:267–280CrossRefPubMedGoogle Scholar
  18. 18.
    Chantry, D., and Burgess, L.E. 2002. Chemokines in allergy. Curr Drug Targets Inflamm Allergy 1:109–116CrossRefPubMedGoogle Scholar
  19. 19.
    Garcia, G., Godot, V., and Humbert, M. 2005. New chemokine targets for asthma therapy. Curr Allergy Asthma Rep 5:155–160CrossRefPubMedGoogle Scholar
  20. 20.
    Kurup, V.P., Raju, R., and Manickam, P. 2005. Profile of gene expression in a murine model of allergic bronchopulmonary aspergillosis. Infect Immun 73:4381–4384CrossRefPubMedGoogle Scholar
  21. 21.
    Hogaboam, C.M., et al. 1999. Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis. J Immunol 162:6071–6079PubMedGoogle Scholar
  22. 22.
    Schuh, J.M., Blease, K., Kunkel, S.L., and Hogaboam, C.M. 2002. Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses to Aspergillus fumigatus. Am J Physiol Lung Cell Mol Physiol 283:L198–204PubMedGoogle Scholar
  23. 23.
    Hogaboam, C.M., Blease, K., and Schuh, J.M. 2003. Cytokines and chemokines in allergic bronchopulmonary aspergillosis (ABPA) and experimental Aspergillus-induced allergic airway or asthmatic disease. Front Biosci 8:e147–156CrossRefPubMedGoogle Scholar
  24. 24.
    Mehrad, B., Moore, T.A., and Standiford, T.J. 2000. Macrophage inflammatory protein-1 alpha is a critical mediator of host defense against invasive pulmonary aspergillosis in neutro-penic hosts. J Immunol 165:962–968PubMedGoogle Scholar
  25. 25.
    Buckland, K.F., and Hogaboam, C.M. 2006. Cytokine and chemokine responses in fungal allergy. Research Signpost 37:288–308Google Scholar
  26. 26.
    Schuh, J.M., Blease, K., and Hogaboam, C.M. 2002. CXCR2 is necessary for the development and persistence of chronic fungal asthma in mice. J Immunol 168:1447–1456PubMedGoogle Scholar
  27. 27.
    Blease, K., et al. 2000. Airway remodeling is absent in CCR1-/- mice during chronic fungal allergic airway disease. J Immunol 165:1564–1572PubMedGoogle Scholar
  28. 28.
    Blease, K., et al. 2000. Enhanced pulmonary allergic responses to Aspergillus in CCR2-/-mice. J Immunol 165:2603–2611PubMedGoogle Scholar
  29. 29.
    Blease, K., et al. 2001. Antifungal and airway remodeling roles for murine monocyte chemoattractant protein-1/CCL2 during pulmonary exposure to Asperigillus fumigatus conidia. J Immunol 166:1832–1842PubMedGoogle Scholar
  30. 30.
    Schuh, J.M., et al. 2002. Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice. Faseb J 16:1313–1315PubMedGoogle Scholar
  31. 31.
    Le Souef, P.N. 2006. Variations in genetic influences on the development of asthma throughout childhood, adolescence and early adult life. Curr Opin Allergy Clin Immunol 6:317–322CrossRefPubMedGoogle Scholar
  32. 32.
    Schuh, J.M., Blease, K., and Hogaboam, C.M. 2002. The role of CC chemokine receptor 5 (CCR5) and RANTES/CCL5 during chronic fungal asthma in mice. Faseb J 16:228–230PubMedGoogle Scholar
  33. 33.
    Buckland, K.F., et al. 2007. Remission of chronic fungal asthma in the absence of CCR8. J Allergy Clin Immunol 119:997–1004CrossRefPubMedGoogle Scholar
  34. 34.
    Lloyd, C.M., and Rankin, S.M. 2003. Chemokines in allergic airway disease. Curr Opin Pharmacol 3:443–448CrossRefPubMedGoogle Scholar
  35. 35.
    Carpenter, K.J., et al. 2005. Therapeutic targeting of CCR1 attenuates established chronic fungal asthma in mice. Br J Pharmacol 145:1160–1172CrossRefPubMedGoogle Scholar
  36. 36.
    Hogaboam, C.M., et al. 2005. The therapeutic potential in targeting CCR5 and CXCR4 receptors in infectious and allergic pulmonary disease. Pharmacol Ther 107:314–328CrossRefPubMedGoogle Scholar
  37. 37.
    Schuh, J.M., et al. 2003. Intrapulmonary targeting of RANTES/CCL5-responsive cells prevents chronic fungal asthma. Eur J Immunol 33:3080–3090CrossRefPubMedGoogle Scholar
  38. 38.
    Blease, K., et al. 2001. IL-13 fusion cytotoxin ameliorates chronic fungal-induced allergic airway disease in mice. J Immunol 167:6583–6592PubMedGoogle Scholar
  39. 39.
    Blease, K., et al. 2002. Stat6-deficient mice develop airway hyperresponsiveness and peribronchial fibrosis during chronic fungal asthma. Am J Pathol 160:481–490PubMedGoogle Scholar
  40. 40.
    Carpenter, K.J., and Hogaboam, C.M. 2005. Immunosuppressive effects of CCL17 on pulmonary antifungal responses during pulmonary invasive aspergillosis. Infect Immunol 73:7198–7207CrossRefGoogle Scholar
  41. 41.
    Tremblay, K., et al. 2006. Association study between the CX3CR1 gene and asthma. Genes Immun 7:632–639CrossRefPubMedGoogle Scholar
  42. 42.
    Panina-Bordignon, P., et al. 2001. The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 107:1357–1364CrossRefPubMedGoogle Scholar
  43. 43.
    Munitz, A., Bachelet, I., and Levi-Schaffer, F. 2006. Reversal of airway inflammation and remodeling in asthma by a bispecific antibody fragment linking CCR3 to CD300a. J Allergy Clin Immunol 118:1082–1089CrossRefPubMedGoogle Scholar
  44. 44.
    Fortin, M., et al. 2006. Effects of antisense oligodeoxynucleotides targeting CCR3 on the airway response to antigen in rats. Oligonucleotides 16:203–212CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  1. 1.Immunology Program, Department of PathologyUniversity of Michigan Medical SchoolAnn ArborUSA

Personalised recommendations