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

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.

SUBMITTER: Geng G

PROVIDER: S-EPMC8044338 | biostudies-literature |

REPOSITORIES: biostudies-literature

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PTBP1 is necessary for dendritic cells to regulate T cells homeostasis and antitumor immunity

Project description:Dendritic cells (DCs) play an important role in innate and adaptive immunity. DCs could sense environment pathogens and tumors, presenting those antigens to T cells. PTBP1, an RNA-binding protein, the function in DCs is unknown. Here, we found PTBP1 specific deficiency in DCs could impair T cell homeostasis. PTBP1 deletion in DCs could enhance antitumor immunity and increase asthma exacerbation. Further studies demonstrate that PTBP1 negatively regulates the induction of a subset of IFN-response genes. These findings revealed the novel functions of PTBP1 in DCs and might be a potential therapeutic target for tumors.

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