Chiu, Tzu-YuanTzu-YuanChiuLo, Chien-HuiChien-HuiLoLin, Yi-HsuanYi-HsuanLinLai, Yun-DiYun-DiLaiLin, Shan-ShanShan-ShanLinFang, Ya-TianYa-TianFangHuang, Wei-SyunWei-SyunHuangHuang, Shen-YanShen-YanHuangTsai, Pei-YuanPei-YuanTsaiYang, Fu-HuaFu-HuaYangChong, Weng ManWeng ManChongWu, Yi-ChiehYi-ChiehWuHSING-CHEN TSAIYA-WEN LIUHsu, Chia-LinChia-LinHsuLiao, Jung-ChiJung-ChiLiaoWang, Won-JingWon-JingWang2023-11-172023-11-172023-09-052399-3642https://scholars.lib.ntu.edu.tw/handle/123456789/637206The 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.en[SDGs]SDG3journal article10.1038/s42003-023-05269-0376701372-s2.0-85169758322https://api.elsevier.com/content/abstract/scopus_id/85169758322