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

SJE Beavitt, KW Harder, JM Kemp, J Jones… - The Journal of …, 2005 - journals.aai.org
SJE Beavitt, KW Harder, JM Kemp, J Jones, C Quilici, F Casagranda, E Lam, D Turner…
The Journal of Immunology, 2005journals.aai.org
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 …
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.
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