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

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 organe...

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Autores principales: 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, Tsai, Hsing-Chen, Liu, Ya-Wen, Hsu, Chia-Lin, Liao, Jung-Chi, Wang, Won-Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480498/
https://www.ncbi.nlm.nih.gov/pubmed/37670137
http://dx.doi.org/10.1038/s42003-023-05269-0
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author 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
Tsai, Hsing-Chen
Liu, Ya-Wen
Hsu, Chia-Lin
Liao, Jung-Chi
Wang, Won-Jing
author_facet 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
Tsai, Hsing-Chen
Liu, Ya-Wen
Hsu, Chia-Lin
Liao, Jung-Chi
Wang, Won-Jing
author_sort Chiu, Tzu-Yuan
collection PubMed
description 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.
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spelling pubmed-104804982023-09-07 INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control 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 Tsai, Hsing-Chen Liu, Ya-Wen Hsu, Chia-Lin Liao, Jung-Chi Wang, Won-Jing Commun Biol Article 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. Nature Publishing Group UK 2023-09-05 /pmc/articles/PMC10480498/ /pubmed/37670137 http://dx.doi.org/10.1038/s42003-023-05269-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Tsai, Hsing-Chen
Liu, Ya-Wen
Hsu, Chia-Lin
Liao, Jung-Chi
Wang, Won-Jing
INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title_full INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title_fullStr INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title_full_unstemmed INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title_short INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control
title_sort inpp5e regulates cd3ζ enrichment at the immune synapse by phosphoinositide distribution control
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480498/
https://www.ncbi.nlm.nih.gov/pubmed/37670137
http://dx.doi.org/10.1038/s42003-023-05269-0
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