title: Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity.
abstract: The etiology of asthma, a chronic inflammatory disorder of the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both a facilitator and inhibitor of signaling pathways that play a role in allergic inflammation, although its role in asthma is unclear because Lyn is not expressed in T cells. We show in the present study that Lyn-/- mice develop a severe, persistent inflammatory asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified bronchospasm, hyper IgE, and Th2-polarizing dendritic cells. Dendritic cells from Lyn-/- mice have a more immature phenotype, exhibit defective inhibitory signaling pathways, produce less IL-12, and can transfer disease when adoptively transferred into wild-type recipients. Our results show that Lyn regulates the intensity and duration of multiple asthmatic traits and indicate that Lyn is an important negative regulator of Th2 immune responses.
authors: Lung Disease Research Group, Department of Medicine, University of Melbourne, Victoria, Australia.
authors: Sarah-Jane E
authors: SJ
authors: Beavitt
authors: Kenneth W
authors: KW
authors: Harder
authors: Joanna M
authors: JM
authors: Kemp
authors: Jessica
authors: J
authors: Jones
authors: Cathy
authors: C
authors: Quilici
authors: Franca
authors: F
authors: Casagranda
authors: Ellen
authors: E
authors: Lam
authors: Debra
authors: D
authors: Turner
authors: Siobhain
authors: S
authors: Brennan
authors: Peter D
authors: PD
authors: Sly
authors: David M
authors: DM
authors: Tarlinton
authors: Gary P
authors: GP
authors: Anderson
authors: Margaret L
authors: ML
authors: Hibbs
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001986:Bronchial Spasm / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000235:genetics; D007073:Immunoglobulin E / Q000502:physiology; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000276:immunology; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D019061:src-Family Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D000485:Allergens; D018836:Inflammation Mediators; D007073:Immunoglobulin E; D010047:Ovalbumin; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases