INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
Journal
Communications Biology
Journal Volume
6
Journal Issue
1
Date Issued
2023-09-05
Author(s)
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
Hsu, Chia-Lin
Liao, Jung-Chi
Wang, Won-Jing
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.
SDGs
Publisher
Nature Research
Type
journal article