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PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity

Dendritic cells (DCs) play an important role in linking innate and adaptive immunity. DCs can sense endogenous and exogenous antigens and present those antigens to T cells to induce an immune response or immune tolerance. During activation, alternative splicing (AS) in DCs is dramatically changed to...

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Autores principales: Geng, Guangfeng, Xu, Changlu, Peng, Nan, Li, Yue, Liu, Jinhua, Wu, Jing, Liang, Jing, Zhu, Yushan, Shi, Lihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044338/
https://www.ncbi.nlm.nih.gov/pubmed/33421118
http://dx.doi.org/10.1111/imm.13304
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author Geng, Guangfeng
Xu, Changlu
Peng, Nan
Li, Yue
Liu, Jinhua
Wu, Jing
Liang, Jing
Zhu, Yushan
Shi, Lihong
author_facet Geng, Guangfeng
Xu, Changlu
Peng, Nan
Li, Yue
Liu, Jinhua
Wu, Jing
Liang, Jing
Zhu, Yushan
Shi, Lihong
author_sort Geng, Guangfeng
collection PubMed
description Dendritic cells (DCs) play an important role in linking innate and adaptive immunity. DCs can sense endogenous and exogenous antigens and present those antigens to T cells to induce an immune response or immune tolerance. During activation, alternative splicing (AS) in DCs is dramatically changed to induce cytokine secretion and upregulation of surface marker expression. PTBP1, an RNA‐binding protein, is essential in alternative splicing, but the function of PTBP1 in DCs is unknown. Here, we found that a specific deficiency of Ptbp1 in DCs could increase MHC II expression and perturb T‐cell homeostasis without affecting DC development. Functionally, Ptbp1 deletion in DCs could enhance antitumour immunity and asthma exacerbation. Mechanistically, we found that Pkm alternative splicing and a subset of Ifn response genes could be regulated by PTBP1. These findings revealed the function of PTBP1 in DCs and indicated that PTBP1 might be a novel therapeutic target for antitumour treatment.
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spelling pubmed-80443382021-04-16 PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity Geng, Guangfeng Xu, Changlu Peng, Nan Li, Yue Liu, Jinhua Wu, Jing Liang, Jing Zhu, Yushan Shi, Lihong Immunology Original Articles Dendritic cells (DCs) play an important role in linking innate and adaptive immunity. DCs can sense endogenous and exogenous antigens and present those antigens to T cells to induce an immune response or immune tolerance. During activation, alternative splicing (AS) in DCs is dramatically changed to induce cytokine secretion and upregulation of surface marker expression. PTBP1, an RNA‐binding protein, is essential in alternative splicing, but the function of PTBP1 in DCs is unknown. Here, we found that a specific deficiency of Ptbp1 in DCs could increase MHC II expression and perturb T‐cell homeostasis without affecting DC development. Functionally, Ptbp1 deletion in DCs could enhance antitumour immunity and asthma exacerbation. Mechanistically, we found that Pkm alternative splicing and a subset of Ifn response genes could be regulated by PTBP1. These findings revealed the function of PTBP1 in DCs and indicated that PTBP1 might be a novel therapeutic target for antitumour treatment. John Wiley and Sons Inc. 2021-02-03 2021-05 /pmc/articles/PMC8044338/ /pubmed/33421118 http://dx.doi.org/10.1111/imm.13304 Text en © 2021 The Authors. Immunology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Geng, Guangfeng
Xu, Changlu
Peng, Nan
Li, Yue
Liu, Jinhua
Wu, Jing
Liang, Jing
Zhu, Yushan
Shi, Lihong
PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title_full PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title_fullStr PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title_full_unstemmed PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title_short PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity
title_sort ptbp1 is necessary for dendritic cells to regulate t‐cell homeostasis and antitumour immunity
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044338/
https://www.ncbi.nlm.nih.gov/pubmed/33421118
http://dx.doi.org/10.1111/imm.13304
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