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* Laboratoire de Physiologie Animale and
Laboratoire d’Allergologie Expérimentale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium;
Laboratory of Cellular and Molecular Physiology, GIGA-Research, and
Laboratoire de Pathologie Animale, Faculté de Médecine Vétérinaire, University of Liège, Liège, Belgium;
¶ Department of Physiology and Immunology, Laboratory of Molecular and Cellular Therapy, Medical School of the Vrije Universiteit Brussel, Brussels, Belgium; and
|| Institut National de la Santé et de la Recherche Médicale Unité 774, Institut Pasteur de Lille, 59019 Lille Cédex, France
Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4+CD25+Foxp3+IL-10+ regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4+ mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 The Laboratory of Cellular and Molecular Physiology is supported by grants from the Fonds National de la Recherche Scientifique (Belgium; Mandat d’Impulsion Scientifique), by the Fonds de la Recherche Scientifique Médicale (Belgium), by the Belgian Programme on Interuniversity Attraction Poles (Fedimmune) initiated by the Belgian State (Belgian Science Policy), and by an Action de Recherche Concertée de la Communauté Française de Belgique. M.M. is a Research Director and D.B. is a Research Fellow at the Fonds National de la Recherche Scientifique. E.H. is a Research Fellow at the Fonds de la Formation à la Recherche dans l’Industrie et l’Agriculture, Belgium.
2 Address correspondence and reprint requests to Dr. Fabrice Bureau, Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, B34, Avenue de l’Hôpital, 1, Sart-Tilman, B-4000, Liège, Belgium. E-mail address: fabrice.bureau{at}ulg.ac.be
3 Abbreviations used in this paper: AHR, airway hyperreactivity; BALF, bronchoalveolar lavage fluid; DC, dendritic cell; BMDC, bone marrow-derived DC; eGFP, enhanced GFP; FHA, Bordetella pertussis filamentous hemagglutinin; i.t., intratracheal(ly); MCh, β-methacholine; MLN, mediastinal lymph node; PAS, periodic acid-Schiff; sRaw, specific airway resistance; MHCII, MHC class II; Ctrl, control; GITR, glucocorticoid-induced TNFR; Treg, regulatory T cell.
4 The online version of this article contains supplemental material.
This article has been cited by other articles:
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  K. D. Nguyen, C. Vanichsarn, and K. C. Nadeau Impaired IL-10-dependent Induction of Tolerogenic Dendritic Cells by CD4+CD25hiCD127lo/- Natural Regulatory T Cells in Human Allergic Asthma Am. J. Respir. Crit. Care Med., November 1, 2009; 180(9): 823 - 833. [Abstract] [Full Text] [PDF]
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 J. D. Campbell, K. F. Buckland, S. J. McMillan, J. Kearley, W. L.G. Oldfield, L. J. Stern, H. Gronlund, M. van Hage, C. J. Reynolds, R. J. Boyton, et al. Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression J. Exp. Med., July 6, 2009; 206(7): 1535 - 1547. [Abstract] [Full Text] [PDF]
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