Surgery (RMH) - Research Publications

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Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity

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 (AMER ASSOC IMMUNOLOGISTS, 2005-08-01)

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.