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The Capicua/ETS Translocation Variant 5 Axis Regulates Liver-Resident …

  • 저널명HEPATOLOGY, 70(1):358-371. doi: 10.1002/hep.30594
    • 담당교수Yoontae Lee
    • 조회467
    • 작성자최고관리자
    • 2020-03-04


    ■ Abstract
    Liver-resident memory T (liver TRM) cells exert protective immune responses following liver infection by malaria parasites. However, how these TRM cells are developed and what the consequence is if they are not properly main-tained remain poorly understood. Here, we show that the transcriptional repressor, Capicua (CIC), controls liver CD8+ TRM cell development to maintain normal liver function. Cic-deficient mice have a greater number of liver CD8+ TRM cells and liver injury phenotypes accompanied by increased levels of proinflammatory cytokine genes in liver tissues. Excessive formation of CD69+CD8+ TRM-like cells was also observed in mice with acetaminophen-in-duced liver injury (AILI). Moreover, expansion of liver CD8+ TRM cell population and liver injury phenotypes in T-cell–specific Cic null mice were rescued by codeletion of ETS translocation variant [Etv]5 alleles, indicating that Etv5 is a CIC target gene responsible for regulation of CD8+ TRM cell development and liver function. We also discovered that ETV5 directly regulates expression of Hobit, a master transcription factor for TRM cell development, in CD8+ T cells. Conclusion: Our findings suggest the CIC-ETV5 axis as a key molecular module that controls CD8+ TRM cell development, indicating a pathogenic role for CD8+ TRM cells in liver injury.