Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen

By Hendrik Jan de Heer, H. Hammad, Thomas Soullié, D. Hijdra, N. Vos, M. Willart, H. Hoogsteden, B. Lambrecht. Journal of Experimental Medicine, 2004

880 citations recorded by the source corpus.

Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/0fed8c8a5b668bb9a4040707cfe80918444cc868

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. H. Hammad
2. B. Lambrecht
3. Yong‐jun Liu
4. G. Trinchieri
5. M. Gilliet
6. F. Tacke
7. G. Randolph
8. Steffen Jung

Citations in the corpus

• Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts (2006, background): “Specifically, T cell priming has been noted when mDCs present FITC-labeled ovalbumin (OVA) protein in an inflammatory airway disease mode”
• Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand (2007, background): “pDCs were shown to suppress infl ammatory responses to inhaled allergens (39), microbial infections (40), and tumors (41), to promote allogeneic stem cell engraftment (42), and to mediate tolerance to solid grafts by inducing T regulatory cells (43).”
• Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen (2010, background): “6) or pDCs, leads to Th2 immunity to inhaled OVA antigen (Lambrecht et al., 2000; Sung et al., 2001; de Heer et al., 2004; Piggott et al., 2005; Matsubara et al., 2006; Krishnamoorthy et al., 2008).”
• In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma (2005, background): “DCs are believed to be the most important APCs in the lung in steady-state (2, 3, 12) and are mainly known for their potential to induce the activation of naive T cells in the draining MLNs leading to antimicrobial, antitumoral, and allergic T cell responses (9, 25, 26).”
• Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells (2007, background): “Myeloid DCs (mDCs) become involved very early in the disease by inducing sensitization to inhaled antige”