Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity
- Author(s)
- Beavitt, SJE; Harder, KW; Kemp, JM; Jones, J; Quilici, C; Casagranda, F; Lam, E; Turner, D; Brennan, S; Sly, PD; Tarlinton, DM; Anderson, GP; Hibbs, ML;
- Details
- Publication Year 2005-08-01,Volume 175,Issue #3,Page 1867-1875
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- ALLERGIC AIRWAY INFLAMMATION; T-CELL-ACTIVATION; TYROSINE KINASE; DENDRITIC CELLS; PIR-B; EOSINOPHILIC INFLAMMATION; IN-VIVO; MUCOSAL IMMUNITY; IL-12 PRODUCTION; FAS RECEPTOR
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Creation Date: 2005-08-01 12:00:00