High-affinity IgE receptors on dendritic cells exacerbate Th2-dependent inflammation.

Abstract

The IgE-mediated and Th2-dependent late-phase reaction remains a mechanistically enigmatic and daunting element of human allergic inflammation. In this study, we uncover the FcεRI on dendritic cells (DCs) as a key in vivo component of this form of allergy. Because rodent, unlike human, DCs lack FcεRI, this mechanism could be revealed only by using a new transgenic mouse model with human-like FcεRI expression on DCs. In the presence of IgE and allergen, FcεRI(+) DCs instructed naive T cells to differentiate into Th2 cells in vitro and boosted allergen-specific Th2 responses and Th2-dependent eosinophilia at the site of allergen exposure in vivo. Thus, FcεRI on DCs drives the cascade of pathogenic reactions linking the initial allergen capture by IgE with subsequent Th2-dominated T cell responses and the development of late-phase allergic tissue inflammation.

• Authors: Eva Sallmann, Bärbel Reininger, Sabine Brandt, Nikolaus Duschek, Elisabeth Hoflehner, Erika Garner-Spitzer, Barbara Platzer, Eleonora Dehlink, Martina Hammer, Martin Holcmann, Hans C Oettgen, Ursula Wiedermann, Maria Sibilia, Edda Fiebiger, Antal Rot, Dieter Maurer
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 187 Issue 1 Pg. 164-71 (Jul 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21622859 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Antigens, Plant
• FcepsilonRI alpha-chain, human
• Inflammation Mediators
• Receptors, IgE
• Bet v 1 allergen, Betula
• Ovalbumin

Topics

• Allergens (toxicity)
• Animals
• Antigens, Plant (toxicity)
• Cells, Cultured
• Coculture Techniques
• Dendritic Cells (immunology, metabolism, pathology)
• Female
• Humans
• Inflammation Mediators (metabolism, physiology, toxicity)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Ovalbumin (toxicity)
• Protein Binding (genetics, immunology)
• Receptors, IgE (deficiency, metabolism, physiology)
• Th2 Cells (immunology, metabolism, pathology)
• Time Factors