PMID- 33421118 OWN - NLM STAT- MEDLINE DCOM- 20211004 LR - 20240226 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 163 IP - 1 DP - 2021 May TI - PTBP1 is necessary for dendritic cells to regulate T-cell homeostasis and antitumour immunity. PG - 74-85 LID - 10.1111/imm.13304 [doi] AB - 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. CI - (c) 2021 The Authors. Immunology published by John Wiley & Sons Ltd. FAU - Geng, Guangfeng AU - Geng G AUID- ORCID: 0000-0002-0518-406X AD - State Key Laboratory of Experimental Hematology, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China. FAU - Xu, Changlu AU - Xu C AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Peng, Nan AU - Peng N AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Li, Yue AU - Li Y AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Liu, Jinhua AU - Liu J AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Wu, Jing AU - Wu J AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Liang, Jing AU - Liang J AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Zhu, Yushan AU - Zhu Y AD - State Key Laboratory of Experimental Hematology, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China. FAU - Shi, Lihong AU - Shi L AD - State Key Laboratory of Experimental Hematology, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China. AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210203 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Cytokines) RN - 0 (Heterogeneous-Nuclear Ribonucleoproteins) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Ptbp1 protein, mouse) RN - 139076-35-0 (Polypyrimidine Tract-Binding Protein) RN - EC 2.7.1.40 (Pkm protein, mouse) RN - EC 2.7.1.40 (Pyruvate Kinase) SB - IM MH - Alternative Splicing MH - Animals MH - Asthma/*enzymology/genetics/immunology/pathology MH - Cell Line, Tumor MH - Cytokines/genetics/metabolism MH - Dendritic Cells/*enzymology/immunology MH - Gene Expression Regulation MH - Heterogeneous-Nuclear Ribonucleoproteins/genetics/*metabolism MH - Histocompatibility Antigens Class II/metabolism MH - Homeostasis MH - Lung/*enzymology/immunology/pathology MH - Lymphocyte Activation MH - Lymphocytes, Tumor-Infiltrating/immunology/*metabolism MH - Melanoma, Experimental/*enzymology/genetics/immunology/metabolism MH - Mice, Knockout MH - Polypyrimidine Tract-Binding Protein/genetics/*metabolism MH - Pyruvate Kinase/genetics/metabolism MH - Skin Neoplasms/*enzymology/genetics/immunology/pathology MH - T-Lymphocytes/immunology/*metabolism MH - Tumor Escape MH - Tumor Microenvironment MH - Mice PMC - PMC8044338 OTO - NOTNLM OT - RNA-binding protein OT - alternative splicing OT - asthma OT - dendritic cells OT - tumour COIS- The authors declare that they have no conflicts of interest. EDAT- 2021/01/10 06:00 MHDA- 2021/10/05 06:00 PMCR- 2021/02/03 CRDT- 2021/01/09 17:09 PHST- 2020/12/18 00:00 [revised] PHST- 2020/08/13 00:00 [received] PHST- 2020/12/19 00:00 [accepted] PHST- 2021/01/10 06:00 [pubmed] PHST- 2021/10/05 06:00 [medline] PHST- 2021/01/09 17:09 [entrez] PHST- 2021/02/03 00:00 [pmc-release] AID - IMM13304 [pii] AID - 10.1111/imm.13304 [doi] PST - ppublish SO - Immunology. 2021 May;163(1):74-85. doi: 10.1111/imm.13304. Epub 2021 Feb 3.