Abstract
Dendritic cells (DCs) are known to play a crucial role in the induction of allergic asthma in mouse models. Their antigen presentation capacity, linked to their capacity to prime naïve T cells and polarize them towards a Th1, Th2, Th17 or Treg profile, allows them to efficiently initiate an immune response to allergens. Airway dendritic cells also play a crucial role in the local restimulation of circulating effector T cells upon allergen challenge. Given their important implication in pathogenesis of asthma in mice models, the study of environmental and pharmacologic effects on DCs function is now a blooming field. There is therefore a critical need for a stable, yet flexible animal model to investigate the effects of various environmental factors (endotoxins, pollutants, etc.) or pharmacologic molecules on DCs and subsequently on their role in asthma pathogenesis. This chapter presents an approach using a reliable animal model of asthma that has the advantage to allow interventions on DCs before their use to induce allergic asthma. We also cover some of the endpoint techniques used to assess asthma and the immune reactions involved in its pathogenesis.
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Banchereau, J. and Steinman, R. M. (1998) Dendritic cells and the control of immunity. Nature 392, 245–252.
GeurtsvanKessel, C. H., and Lambrecht, B. N. (2008) Division of labor between dendritic cell subsets of the lung. Mucosal. Immunol. 1, 442–450.
Hammad, H., and Lambrecht, B. N. (2006) Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J. Allergy Clin. Immunol. 118, 331–336.
Hammad, H., and Lambrecht, B. N. (2008) Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat. Rev. Immunol. 8, 193–204.
Sung, S. S., Fu, S. M., Rose, C. E., Jr., Gaskin, F., Ju, S. T., and Beaty, S. R. (2006) A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J. Immunol. 176, 2161–2172.
Jakubzick, C., Tacke, F., Llodra, J., van, R. N., and Randolph, G. J. (2006) Modulation of dendritic cell trafficking to and from the airways. J. Immunol. 176, 3578–3584.
Vermaelen, K. Y., Carro-Muino, I., Lambrecht, B. N., and Pauwels, R. A. (2001) Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J. Exp. Med. 193, 51–60.
Lambrecht, B. N., and Hammad, H. (2003) Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat. Rev. Immunol. 3, 994–1003.
van Rijt, L. S., Prins, J. B., Leenen, P. J., Thielemans, K., De, V., V, Hoogsteden, H. C., and Lambrecht, B. N. (2002) Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly-6C(neg) bone marrow precursors in a mouse model of asthma. Blood 100, 3663–3671.
van Rijt, L. S., Vos, N., Willart, M., Kleinjan, A., Coyle, A. J., Hoogsteden, H. C., and Lambrecht, B. N. (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.
van Rijt, L. S., Jung, S., Kleinjan, A., Vos, N., Willart, M., Duez, C., Hoogsteden, H. C., and Lambrecht, B. N. (2005) In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J. Exp. Med. 201, 981–991.
de Heer, H. J., Hammad, H., Soullie, T., Hijdra, D., Vos, N., Willart, M. A., Hoogsteden, H. C., and Lambrecht, B. N. (2004) Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 200, 89–98.
de Heer, H. J., Hammad, H., Kool, M., and Lambrecht, B. N. (2005) Dendritic cell subsets and immune regulation in the lung. Semin. Immunol. 17, 295–303.
Eisenbarth, S. C., Piggott, D. A., Huleatt, J. W., Visintin, I., Herrick, C. A., and Bottomly, K. (2002) Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645–1651.
Kuipers, H., Hijdra, D., De, V., V, Hammad, H., Prins, J. B., Coyle, A. J., Hoogsteden, H. C., and Lambrecht, B. N. (2003) Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells. J. Immunol. 171, 3645–3654.
Kohl, J., Baelder, R., Lewkowich, I. P., Pandey, M. K., Hawlisch, H., Wang, L., Best, J., Herman, N. S., Sproles, A. A., Zwirner, J., Whitsett, J. A., Gerard, C., Sfyroera, G., Lambris, J. D., and Wills-Karp, M. (2006) A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. J. Clin. Invest. 116, 783–796.
Stampfli, M. R., Wiley, R. E., Neigh, G. S., Gajewska, B. U., Lei, X. F., Snider, D. P., Xing, Z., and Jordana, M. (1998) GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice. J. Clin. Invest. 102, 1704–1714.
Hammad, H., de Heer, H. J., Soullie, T., Hoogsteden, H. C., Trottein, F., and Lambrecht, B. N. (2003) Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1. J. Immunol. 171, 3936–3940.
Lambrecht, B. N., Pauwels, R. A., and Fazekas De St, G. B. (2000) Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model. J. Immunol. 164, 2937–2946.
Brasel, K., De, S. T., Smith, J. L., and Maliszewski, C. R. (2000) Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures. Blood 96, 3029–3039.
Lutz, M. B., Kukutsch, N., Ogilvie, A. L., Rossner, S., Koch, F., Romani, N., and Schuler, G. (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods 223, 77–92.
Lambrecht, B. N., De, V. M., Coyle, A. J., Gutierrez-Ramos, J. C., Thielemans, K., and Pauwels, R. A. (2000) Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J. Clin. Invest 106, 551–559.
Sung, S., Rose, C. E., and Fu, S. M. (2001) Intratracheal priming with ovalbumin- and ovalbumin 323–339 peptide-pulsed dendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation. J. Immunol. 166, 1261–1271.
Kleinjan, A., Willart, M., van Rijt, L. S., Braunstahl, G. J., Leman, K., Jung, S., Hoogsteden, H. C., and Lambrecht, B. N. (2006) An essential role for dendritic cells in human and experimental allergic rhinitis. J. Allergy Clin. Immunol. 118, 1117–1125.
Hammad, H., Lambrecht, B. N., Pochard, P., Gosset, P., Marquillies, P., Tonnel, A. B., and Pestel, J. (2002) Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: involvement of CCR7. J. Immunol. 169, 1524–1534.
van Rijt, L. S., Kuipers, H., Vos, N., Hijdra, D., Hoogsteden, H. C., and Lambrecht, B. N. (2004) A rapid flow cytometric method for determining the cellular composition of bronchoalveolar lavage fluid cells in mouse models of asthma. J. Immunol. Methods 288, 111–121.
Hammad, H., De, V., V, Maldonado-Lopez, R., Moser, M., Maliszewski, C., Hoogsteden, H. C., and Lambrecht, B. N. (2004) Differential capacity of CD8+ alpha or CD8− alpha dendritic cell subsets to prime for eosinophilic airway inflammation in the T-helper type 2-prone milieu of the lung. Clin. Exp. Allergy 34, 1834–1840.
Kuipers, H., Soullie, T., Hammad, H., Willart, M., Kool, M., Hijdra, D., Hoogsteden, H. C., and Lambrecht, B. N. (2009) Sensitization by intratracheally injected dendritic cells is independent of antigen presentation by host antigen-presenting cells. J. Leukoc. Biol. 85, 64–70.
Hammad, H., de Heer, H. J., Soullie, T., Angeli, V., Trottein, F., Hoogsteden, H. C., and Lambrecht, B. N. (2004) Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am. J. Pathol. 164, 263–271.
Idzko, M., Hammad, H., van, N. M., Kool, M., Muller, T., Soullie, T., Willart, M. A., Hijdra, D., Hoogsteden, H. C., and Lambrecht, B. N. (2006) Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. J. Clin. Invest. 116, 2935–2944.
Hammad, H., Kool, M., Soullie, T., Narumiya, S., Trottein, F., Hoogsteden, H. C., and Lambrecht, B. N. (2007) Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells. J. Exp. Med. 204, 357–367.
Idzko, M., Hammad, H., van, N. M., Kool, M., Vos, N., Hoogsteden, H. C., and Lambrecht, B. N. (2007) Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. J. Clin. Invest. 117, 464–472.
Idzko, M., Hammad, H., van, N. M., Kool, M., Willart, M. A., Muskens, F., Hoogsteden, H. C., Luttmann, W., Ferrari, D., Di, V. F., Virchow, J. C., Jr., and Lambrecht, B. N. (2007) Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat. Med. 13, 913–919.
Smits, H. H., Hammad, H., van, N. M., Soullie, T., Willart, M. A., Lievers, E., Kadouch, J., Kool, M., Kos-van, O. J., Deelder, A. M., Lambrecht, B. N., and Yazdanbakhsh, M. (2007) Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection. J. Allergy Clin. Immunol. 120, 932–940.
Pichavant, M., Goya, S., Hamelmann, E., Gelfand, E. W., and Umetsu, D. T. (2007) Animal models of airway sensitization. Curr. Protoc. Immunol. Chapter 15, Unit-15.18.
Acknowledgments
We would like to thank the Department of Pulmonary Medicine at the Erasmus MC, Rotterdam, The Netherlands for their implication in setting or optimizing many of these experimental protocols.
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Pouliot, P., Willart, M.A., Hammad, H., Lambrecht, B.N. (2010). Studying the Function of Dendritic Cells in Mouse Models of Asthma. In: Naik, S. (eds) Dendritic Cell Protocols. Methods in Molecular Biology, vol 595. Humana Press. https://doi.org/10.1007/978-1-60761-421-0_22
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DOI: https://doi.org/10.1007/978-1-60761-421-0_22
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