Tespa1 negatively regulates Fc epsilon RI-mediated signaling and the mast cell-mediated allergic response

文献类型： 外文期刊

第一作者： Wang, Di

作者： Wang, Di;Zheng, Mingzhu;Qiu, Yuanjun;Guo, Chuansheng;Lei, Lei;Liang, Jingjing;Lou, Jun;Huang, Wei;Dong, Bowen;Wang, Jianli;Cao, Xuetao;Lu, Linrong;Wang, Di;Zheng, Mingzhu;Qiu, Yuanjun;Guo, Chuansheng;Lei, Lei;Zhang, Xue;Liang, Jingjing;Lou, Jun;Huang, Wei;Dong, Bowen;Ke, Yuehai;Lu, Linrong;Zhang, Xue;Ke, Yuehai;Zhou, Yi Ting;Ji, Jian;Wu, Songquan;Cao, Xuetao;Cao, Xuetao

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期刊名称：JOURNAL OF EXPERIMENTAL MEDICINE （ 影响因子：14.307； 五年影响因子：14.851 ）

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收录情况： SCI

摘要： Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via Fc. RI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-gamma 1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly.

分类号： R

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