1. INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
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Tzu-Yuan Chiu, Chien-Hui Lo, Yi-Hsuan Lin, Yun-Di Lai, Shan-Shan Lin, Ya-Tian Fang, Wei-Syun Huang, Shen-Yan Huang, Pei-Yuan Tsai, Fu-Hua Yang, Weng Man Chong, Yi-Chieh Wu, Hsing-Chen Tsai, Ya-Wen Liu, Chia-Lin Hsu, Jung-Chi Liao, and Won-Jing Wang
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Biology (General) ,QH301-705.5 - Abstract
Abstract 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.
- Published
- 2023
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