INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.

Autor: Chiu TY; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan.; The Scripps Research Institute, La Jolla, 92037, USA., Lo CH; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Lin YH; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Lai YD; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Lin SS; Institute of Molecular Medicine, National Taiwan University, Taipei, 10002, Taiwan., Fang YT; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan., Huang WS; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Huang SY; Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Tsai PY; Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Yang FH; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan., Chong WM; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan., Wu YC; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan., Tsai HC; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.; Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100233, Taiwan., Liu YW; Institute of Molecular Medicine, National Taiwan University, Taipei, 10002, Taiwan., Hsu CL; Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan., Liao JC; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan. jungchiliao@gmail.com.; Syncell Inc., Taipei, 115202, Taiwan. jungchiliao@gmail.com., Wang WJ; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan. wangwj@nycu.edu.tw.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Sep 05; Vol. 6 (1), pp. 911. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.1038/s42003-023-05269-0
Abstrakt: 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)P 2 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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