title: IL-33-activated dendritic cells are critical for allergic airway inflammation.
abstract: IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1b, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation.
authors.affiliation: University of Orleans, Molecular Immunology and Embryology, Orleans, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.forename: Noëlline
authors.initials: N
authors.lastname: Guillou
authors.forename: François
authors.initials: F
authors.lastname: Erard
authors.forename: Valérie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000473:pathology; D011014:Pneumonia; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin