한빛사 논문
Sungjun Park1,*, Jiho Park1, Eunjeong Kim1, and Yoontae Lee1,2,*
1 Department of Life Sciences, 2 Division of Integrative Bioscience and Biotechnology, PohangUniversity of Science and Technology (POSTECH), Pohang, Kyungbuk 37673, Republic of Korea
*Corresponding authors,
Sungjun Park, Room 384, POSTECH Biotech Center, 77 Cheongam-Ro,Nam-Gu,Pohang, Gyeongbuk37673, Republic of Korea
Yoontae Lee, Room 388, POSTECH Biotech Center, 77Cheongam-Ro,Nam-Gu,Pohang, Gyeongbuk37673, Republic of Korea
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 is the consequence 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 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, the expansion of liver CD8+ TRM cell population and the liver injury phenotypes in T cell‐specific Cic null mice were rescued by co‐deletion of Etv5 alleles, indicating that Etv5 is a CIC target gene responsible for the regulation of CD8+ TRM cell development and liver function. We also discovered that ETV5 directly regulates the expression of Hobit, a master transcription factor for TRM cell development, in CD8+ T cells.
Conclusion
Our findings not only suggest that the CIC‐ETV5 axis is a key molecular module that controls CD8+ TRM cell development, but also uncover a previously‐unrecognized pathogenic role for CD8+ TRM cells in liver injury.
Keywords: Pro-inflammatory cytokine, Alanine transaminase, Acetaminophen-induced liver injury, Immunopathogenesis, Homolog of Blimp-1 in Tcell (HOBIT)
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