TY - JOUR
T1 - Lyn-Deficient Mice Develop Severe, Persistent Asthma: Lyn Is a Critical Negative Regulator of Th2 Immunity
AU - Beavitt, S.J.E.
AU - Harder, K.W.
AU - Kemp, J.M.
AU - Jones, J.
AU - Quilici, C.
AU - Casagranda, F.
AU - Lam, E.
AU - Turner, Debra
AU - Brennan, Siobhan
AU - Sly, Peter
AU - Tarlinton, D.M.
AU - Anderson, G.P.
AU - Hibbs, M.L.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.4049/jimmunol.175.3.1867
DO - 10.4049/jimmunol.175.3.1867
M3 - Article
VL - 175
SP - 1867
EP - 1875
JO - The Journal of Immunology
JF - The Journal of Immunology
SN - 0022-1767
IS - 3
ER -