ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8 + T Cell Effector and Memory Responses.

Autor:	Sin JH; Division of Pediatric Rheumatology, University of California San Francisco, San Francisco, CA.; Department of Pediatrics, University of California San Francisco, San Francisco, CA.; Biomedical Sciences Graduate Program, University of California, San Francisco, CA., Kashyap S; Division of Pediatric Rheumatology, University of California San Francisco, San Francisco, CA.; Department of Pediatrics, University of California San Francisco, San Francisco, CA., Acenas D; Diabetes Center, University of California, San Francisco, San Francisco, CA., Cortez JT; Diabetes Center, University of California, San Francisco, San Francisco, CA., Lee J; Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.; Department of Medicine, University of California San Francisco, San Francisco, CA., Marson A; Biomedical Sciences Graduate Program, University of California, San Francisco, CA.; Diabetes Center, University of California, San Francisco, San Francisco, CA.; J. David Gladstone Institutes, San Francisco, CA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA.; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.; Chan Zuckerberg Biohub, San Francisco, CA; and., Matloubian M; Department of Medicine, University of California San Francisco, San Francisco, CA.; Division of Rheumatology, University of California San Francisco, San Francisco, CA., Waterfield MR; Division of Pediatric Rheumatology, University of California San Francisco, San Francisco, CA; michael.waterfield@ucsf.edu.; Department of Pediatrics, University of California San Francisco, San Francisco, CA.; Biomedical Sciences Graduate Program, University of California, San Francisco, CA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Mar 01; Vol. 208 (5), pp. 1155-1169. Date of Electronic Publication: 2022 Feb 02.
DOI:	10.4049/jimmunol.2100996
Abstrakt:	CD8 + T cells are critical for the immune response to pathogens and tumors, and CD8 + T cell memory protects against repeat infections. In this study, we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of CD8 + T cell immune responses. Mice with a T cell-specific deletion of ATF7ip have a CD8 + T cell-intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced effector and memory responses. Chromatin immunoprecipitation sequencing studies identified ATF7ip as a repressor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 at the Il7r gene and Il2-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the IL7r locus and the Il2-Il21 intergenic region, indicating that ATF7ip silencing of transposable elements is important for regulating CD8 + T cell function. These results demonstrate a new epigenetic pathway by which IL-7R and IL-2 production are constrained in CD8 + T cells, and this may open up new avenues for modulating their production. (Copyright © 2022 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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