Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation.
Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation.
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DOI：
10.1016/j.immuni.2009.02.008
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发表时间：
2009-04-17
期刊：
影响因子：
32.4
通讯作者：
Rivera, Juan
中科院分区：
文献类型：
--
作者：
Charles, Nicolas;Watford, Wendy T.;Ramos, Haydee L.;Hellman, Lars;Oettgen, Hans C.;Gomez, Gregorio;Ryan, John J.;O'Shea, John J.;Rivera, Juan
TH 1/TH 2平衡是宿主防御的关键，其失调具有病理生理学后果。嗜碱性粒细胞在TH 2分化中是重要的。然而，控制嗜碱性粒细胞介导的TH 2分化的发生和程度的因素是未知的。在这里，我们证明了林恩激酶抑制嗜碱性粒细胞加塔-3的表达和TH 2分化的起始和程度。Lyn-null小鼠具有显著的嗜碱性粒细胞增多，这是一种组成性TH 2偏斜，在嗜碱性粒细胞体内激发后加剧，产生针对正常惰性抗原的抗体，并且未能对TH 1病原体做出适当反应。TH 2的偏移依赖于嗜碱性粒细胞，IgE和IL-4，但不依赖于肥大细胞。我们的研究结果表明，嗜碱性细胞表达的林恩激酶发挥调节控制TH 2的分化和功能。
TH1/TH2 balance is key to host defense and its dysregulation has pathophysiological consequences. Basophils are important in TH2 differentiation. However, the factors controlling the onset and extent of basophil-mediated TH2 differentiation are unknown. Here, we demonstrate that Lyn kinase dampens basophil GATA-3 expression and the initiation and extent of TH2 differentiation. Lyn-null mice had a marked basophilia, a constitutive TH2 skewing that was exacerbated upon in vivo challenge of basophils, produced antibodies to a normally inert antigen, and failed to appropriately respond to a TH1 pathogen. The TH2 skewing was dependent on basophils, IgE and IL-4, but was independent of mast cells. Our findings demonstrate that basophil-expressed Lyn kinase exerts regulatory control on TH2 differentiation and function.
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影响因子：
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作者：
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