RNA-binding protein PCBP1 shapes tolerance and immune response by constraining the formation of regulatory T cells
| Autor: | Ephraim Abrokwa Ansa-Addo, Huai-Cheng Huang, Supinya Iamsawat, Xue-Zhong Yu, Philip H Howe, Zihai Li |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:57.12-57.12 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.202.supp.57.12 |
| Popis: | Maintaining adequate regulatory T cell (Treg) and effector T cell balance is critical for efficient regulation of tolerance and immune response, respectively. There is increasing evidence that in addition to regulating RNA fate, RNA-binding proteins (RBPs) may also control gene expression and determine the fate of immune cells. Here by studying mice in which the RBP Pcbp1 gene was disrupted in T cells, we define PCBP1 as a global regulator of immune activity that stabilizes immune responses, while repressing the signature programs of Tregs. PCBP1 expression was upregulated in response to T cell activation, but functionally inhibited by TGF-β-mediated phosphorylation. Loss of PCBP1 expression in T cells was associated with dysregulated peripheral homeostasis and impaired effector functions in knockout mice. Indeed, PCBP1-deficient T cells produced less IFN-γ and TNF-α upon stimulation with PMA, plus ionomycin, compared to wild-type littermates. Strikingly, lack of PCBP1 constrained the pathogenicity of effector T cells by conferring resistance to acute graft-vs-host disease in mice. Mechanistically, assessment of the genome-wide function of PCBP1 revealed that it limits the expression of genes associated with commitment to the Treg lineage. Consequently, its absence resulted in a marked increase in the frequency of Foxp3+Treg cells. Together, our findings identify PCBP1 as a distinct regulator of effector T cell functions and the formation of Treg cells in order to control the balance between tolerance and immunity. |
| Databáze: | OpenAIRE |
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