In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma

By Leonie S van Rijt, Steffen Jung, A. KleinJan, N. Vos, M. Willart, C. Duez, H. Hoogsteden, B. Lambrecht. Journal of Experimental Medicine, 2005

699 citations recorded by the source corpus.

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell–mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4+ T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c+ DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c+ cells, endogenous or adoptively transferred CD4+ Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c+ DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.

Subfields: Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/e2bc63b4b3dfa30aaf4e66556cd612f6207e72dc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Steffen Jung
2. H. Hammad
3. B. Lambrecht
4. TA Wynn
5. P. Murray
6. F. Geissmann
7. C. Varol
8. M. Willart

In Physiology

1. H. Hammad
2. B. Lambrecht
3. Steffen Jung
4. TA Wynn

Citations in the corpus

• Monocytes give rise to mucosal, but not splenic, conventional dendritic cells (2007, background): “To extend our analysis to another nonlymphoid organ, we studied the lung parenchyma of CD11c-DTR transgenic recipient mice that were depleted of lung DCs by intra-tracheal DTx instillation (26).”
• Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma (2008, background): “A functional role for DCs in the secondary immune response is further supported by the fact that their depletion at the time of allergen challenge abrogates all the characteristic features of asthm”
• Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages (2012, background): “…of DCs by administration of diphtheria toxin A also leads to depletion of other cell types, including tissue-resident, marginal zone, and metallophilic macrophages, NK cells, and NKT cells, as well as some CD11c+ B and T cells (van Rijt et al., 2005; Bennett and Clausen, 2007; Hume, 2011).”
• Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells (2007, background): “Increasingly, mDCs are also viewed as essential pro-inflammatory cells that induce effector cytokine production in primed Th2 cells during airway inflammatio”
• Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen (2010, background): “Although this report is the first one demonstrating that depletion of DCs abolishes Th2 priming to inhaled HDM antigen, we have previously demonstrated that DCs are also crucial for mounting a secondary Th2 immune response to inhaled OVA antigen (Lambrecht et al., 1998; van Rijt et al., 2005).”
• The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. (2008, background): “Once in the tissues, Th2 cells interact with IgE-bearing local DC to increase IL-4, IL-5, IL-9, and IL-13 production [90–92,96–102].”
• Protective and pathogenic functions of macrophage subsets (2011, background): “Nevertheless, other studies have questioned the importance of macrophages in the development of allergic airway disease and instead support a role for another type of mononuclear phagocyte, CD11c + DCs, in the development of eosinophilic inflammation and T H 2-associated cytokine production in the ”
• Mechanisms of Cisplatin Nephrotoxicity (2010, background): “In response to pathogens or products of tissue injury, dendritic cells mature and initiate immunity or inflammatory diseases [194,195].”