title: Interferon response factor-3 promotes the pro-Th2 activity of mouse lung CD11b+conventional dendritic cells in response to house dust mite allergens.
abstract: Very few transcription factors have been identified that are required by antigen-presenting cells (APCs) to induce T helper type 2 (Th2) responses. Because lung CD11b+conventional dendritic cells (CD11b+cDCs) are responsible for priming Th2 responses in house-dust mite (HDM)-induced airway allergy, we used them as a model to identify transcriptional events regulating the pro-Th2 activity of cDCs. Transcriptomic profiling of lung CD11b+cDCs exposed to HDM in vivo revealed first that HDM triggers an antiviral defence-like response, and second that the majority of HDM-induced transcriptional changes depend on the transcription factor Interferon Response Factor-3 (Irf3). Validating the functional relevance of these observations, Irf3-deficient CD11b+cDCs displayed reduced pro-allergic activity. Indeed, Irf3-deficient CD11b+cDCs induced less Th2, more regulatory T cell, and similar Th1 differentiation in naïve CD4+T cells compared to their wild-type counterparts. The altered APC activity of Irf3 CD11b+cDCs was associated with reduced expression of CD86 and was phenocopied by blocking CD86 activity in wild-type CD11b+cDCs. Altogether, these results establish Irf3, known mostly for its role in antiviral responses, as a transcription factor involved in the induction of Th2 responses through the promotion of pro-Th2 costimulation in CD11b+DCs.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Janss
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Mesnil
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Pirottin
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lemaitre
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.affiliation: Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. christophe.desmet@ulg.ac.be.
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Desmet
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D010641:Phenotype; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D039481:CD11b Antigen; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D014157:Transcription Factors
keywords: Allergy; Dendritic cell; House dust mite; Interferon response factor 3; Th2; Transcription factor