title: Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation.
abstract: Runx3 transcription factor regulates cell lineage decisions in thymopoiesis and neurogenesis. Here we report that Runx3 knockout (KO) mice develop spontaneous eosinophilic lung inflammation associated with airway remodeling and mucus hypersecretion. Runx3 is specifically expressed in mature dendritic cells (DC) and mediates their response to TGF-beta. In the absence of Runx3, DC become insensitive to TGF-beta-induced maturation inhibition, and TGF-beta-dependent Langerhans cell development is impaired. Maturation of Runx3 KO DC is accelerated and accompanied by increased efficacy to stimulate T cells and aberrant expression of beta2-integrins. Lung alveoli of Runx3 KO mice accumulate DC characteristic of allergic airway inflammation. Taken together, abnormalities in DC function and subset distribution may constitute the primary immune system defect, which leads to the eosinophilic lung inflammation in Runx3 KO mice. These data may help elucidate the molecular mechanisms underlying the pathogenesis of allergic airway inflammation in humans.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Fainaru
authors.forename: Eilon
authors.initials: E
authors.lastname: Woolf
authors.forename: Joseph
authors.initials: J
authors.lastname: Lotem
authors.forename: Merav
authors.initials: M
authors.lastname: Yarmus
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Dalia
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.forename: Yael
authors.initials: Y
authors.lastname: Bernstein
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018821:CD18 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D018821:CD18 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta