title: 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.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Sallmann
authors.forename: Bärbel
authors.initials: B
authors.lastname: Reininger
authors.forename: Sabine
authors.initials: S
authors.lastname: Brandt
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Duschek
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hoflehner
authors.forename: Erika
authors.initials: E
authors.lastname: Garner-Spitzer
authors.forename: Barbara
authors.initials: B
authors.lastname: Platzer
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dehlink
authors.forename: Martina
authors.initials: M
authors.lastname: Hammer
authors.forename: Martin
authors.initials: M
authors.lastname: Holcmann
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.forename: Edda
authors.initials: E
authors.lastname: Fiebiger
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Dieter
authors.initials: D
authors.lastname: Maurer
mesh_terms: D000485:Allergens / Q000633:toxicity; D000818:Animals; D052179:Antigens, Plant / Q000633:toxicity; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000633:toxicity; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C543355:FcepsilonRI alpha-chain, human; D018836:Inflammation Mediators; D017455:Receptors, IgE; C061312:Bet v 1 allergen, Betula; D010047:Ovalbumin