Signal-transducing adaptor protein-2 has a nonredundant role for IL-33-triggered mast cell activation
Signal-transducing adaptor protein-2 has a nonredundant role for IL-33-triggered mast cell activation
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信号转导接头蛋白 2 对 IL-33 触发的肥大细胞激活具有非冗余作用
DOI：
10.1016/j.bbrc.2021.07.098
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发表时间：
2021
影响因子：
3.1
通讯作者：
Tadashi
中科院分区：
文献类型：
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作者：
Kashiwakura;Jun-ichi; Koizumi;Nao; Saitoh;Kodai; Kagohashi;Kota; Sasaki;Yuto; Kobayashi;Fuki; Kawahara;Shoya; Yamauchi;Yukie; Kitai;Yuichi; Muromoto;Ryuta; Oritani;Kenji; Matsuda;Tadashi
信号转导衔接蛋白（STAP）-2是STAP家族衔接蛋白之一，广泛表达于多种细胞中。尽管STAP-2是肥大细胞中FcεRI信号转导的修饰所必需的，但STAP-2在肥大细胞功能中的其他参与尚不清楚。在本研究中，我们主要研究STAP-2在IL-33诱导的肥大细胞活化中的功能作用。在STAP-2缺陷型肥大细胞中，IL-33诱导的IL-6和TNF-α的产生与野生型肥大细胞相比显著降低，但STAP-1缺陷型肥大细胞则无此作用。此外，STAP-2缺陷大大降低了TLR 4介导的肥大细胞活化和细胞因子产生。其机制为IL-33刺激后STAP-2直接与IKKα结合，导致NF-κB活性升高。总之，STAP-2，而不是STAP-1，参与IL-33诱导的肥大细胞活化。
Signal-transducing adaptor protein (STAP)-2 is one of the STAP family adaptor proteins and ubiquitously expressed in a variety types of cells. Although STAP-2 is required for modification of FcεRI signal transduction in mast cells, other involvement of STAP-2 in mast cell functions is unknown, yet. In the present study, we mainly investigated functional roles of STAP-2 in IL-33-induced mast cell activation. In STAP-2-deficient, but not STAP-1-deficient, mast cells, IL-33-induced IL-6 and TNF-α production was significantly decreased compared with that of wild-type mast cells. In addition, STAP-2-deficiency greatly reduced TLR4-mediated mast cell activation and cytokine production. For the mechanisms, STAP-2 directly binds to IKKα after IL-33 stimulation, leading to elevated NF-κB activity. In conclusion, STAP-2, but not STAP-1, participates in IL-33-induced mast cells activation.