title: A critical role for dendritic cells in the evolution of IL-1β-mediated murine airway disease.
abstract: Chronic airway inflammation and fibrosis, known as airway remodeling, are defining features of chronic obstructive pulmonary disease and are refractory to current treatments. How and whether chronic inflammation contributes to airway fibrosis remain controversial. In this study, we use a model of chronic obstructive pulmonary disease airway disease utilizing adenoviral delivery of IL-1β to determine that adaptive T cell immunity is required for airway remodeling because mice deficient in α/β T cells (tcra(-/-)) are protected. Dendritic cells (DCs) accumulate around chronic obstructive pulmonary disease airways and are critical to prime adaptive immunity, but they have not been shown to directly influence airway remodeling. We show that DC depletion or deficiency in the crucial DC chemokine receptor ccr6 both protect from adenoviral IL-1β-induced airway adaptive T cell immune responses and fibrosis in mice. These results provide evidence that chronic airway inflammation, mediated by accumulation of α/β T cells and driven by DCs, is critical to airway fibrosis.
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Mitsuo
authors: M
authors: Hashimoto
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Haruhiko
authors: H
authors: Yanagisawa
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Shunsuke
authors: S
authors: Minagawa
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Debasish
authors: D
authors: Sen
authors: Department of Medicine, University of California, San Francisco, San Francisco, CA 94110.
authors: Amanda
authors: A
authors: Goodsell
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Royce
authors: R
authors: Ma
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Catherine
authors: C
authors: Moermans
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Kate J
authors: KJ
authors: McKnelly
authors: Department of Medicine, University of California, San Francisco, San Francisco, CA 94110.
authors: Jody L
authors: JL
authors: Baron
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and.
authors: Matthew F
authors: MF
authors: Krummel
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110; and stephen.nishimura@ucsf.edu.
authors: Stephen L
authors: SL
authors: Nishimura
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016693:Receptors, Antigen, T-Cell, alpha-beta