The Capicua/ETS Translocation Variant 5 Axis Regulates Liver‐Resident Memory CD8+ T‐Cell Development and the Pathogenesis of Liver Injury. Issue 1 (25th April 2019)

• Record Type: Journal Article
• Authors: Park, Sungjun; Park, Jiho; Kim, Eunjeong; Lee, Yoontae
• Is Part Of: Hepatology. Volume 70:Issue 1(2019)
• Page Start: 358
• Page End: 371
• Publication Date: 2019-04-25
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.30594
• Languages: English
• ISSNs: 0270-9139

Abstract

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 maintained 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‐induced 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.