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PTBP1 is necessary for dendritic cells to regulate T-cell homeostasis and antitumour immunity.
- Source :
-
Immunology [Immunology] 2021 May; Vol. 163 (1), pp. 74-85. Date of Electronic Publication: 2021 Feb 03. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)
- Subjects :
- Alternative Splicing
Animals
Asthma genetics
Asthma immunology
Asthma pathology
Cell Line, Tumor
Cytokines genetics
Cytokines metabolism
Dendritic Cells immunology
Gene Expression Regulation
Heterogeneous-Nuclear Ribonucleoproteins genetics
Histocompatibility Antigens Class II metabolism
Homeostasis
Lung immunology
Lung pathology
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating immunology
Melanoma, Experimental genetics
Melanoma, Experimental immunology
Melanoma, Experimental metabolism
Mice, Knockout
Polypyrimidine Tract-Binding Protein genetics
Pyruvate Kinase genetics
Pyruvate Kinase metabolism
Skin Neoplasms genetics
Skin Neoplasms immunology
Skin Neoplasms pathology
T-Lymphocytes immunology
Tumor Escape
Tumor Microenvironment
Mice
Asthma enzymology
Dendritic Cells enzymology
Heterogeneous-Nuclear Ribonucleoproteins metabolism
Lung enzymology
Lymphocytes, Tumor-Infiltrating metabolism
Melanoma, Experimental enzymology
Polypyrimidine Tract-Binding Protein metabolism
Skin Neoplasms enzymology
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2567
- Volume :
- 163
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33421118
- Full Text :
- https://doi.org/10.1111/imm.13304