https://scholars.lib.ntu.edu.tw/handle/123456789/637206
標題: | INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control | 作者: | Chiu, Tzu-Yuan Lo, Chien-Hui Lin, Yi-Hsuan Lai, Yun-Di Lin, Shan-Shan Fang, Ya-Tian Huang, Wei-Syun Huang, Shen-Yan Tsai, Pei-Yuan Yang, Fu-Hua Chong, Weng Man Wu, Yi-Chieh HSING-CHEN TSAI YA-WEN LIU Hsu, Chia-Lin Liao, Jung-Chi Wang, Won-Jing |
公開日期: | 5-九月-2023 | 出版社: | Nature Research | 卷: | 6 | 期: | 1 | 來源出版物: | Communications Biology | 摘要: | The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637206 | ISSN: | 2399-3642 | DOI: | 10.1038/s42003-023-05269-0 |
顯示於: | 分子醫學研究所 |
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