Cutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T Cells.

Journal of immunology (Baltimore, Md. : 1950) 2023 Sep 01

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CTL differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. In this study, we show that polycomb repressive complex 1 subunit chromobox (Cbx)4 favors effector CTL differentiation in a murine model. Cbx4 deficiency in CTLs induced a transcriptional signature of memory cells and increased the memory CTL population during acute viral infection. It has previously been shown that besides binding to H3K27me3 through its chromodomain, Cbx4 functions as a small ubiquitin-like modifier (SUMO) E3 ligase in a SUMO-interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in an SIM-dependent way and partially through its chromodomain. Our data suggest a novel role of a polycomb group protein Cbx4 controlling CTL differentiation and indicated SUMOylation as a key molecular mechanism connected to chromatin modification in this process. Copyright © 2023 by The American Association of Immunologists, Inc.

Citation

Guilherme A Melo, Tianhao Xu, Carolina Calôba, Alexander Schutte, Thaís O Passos, Moisés A N Neto, Gabrielle Brum, Bárbara Oliveira-Vieira, Luiza Higa, Fábio L L Monteiro, Luiz Berbert, André N A Gonçalves, Amilcar Tanuri, João P B Viola, Miriam B F Werneck, Helder I Nakaya, Matthew E Pipkin, Gustavo J Martinez, Renata M Pereira. Cutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T Cells. Journal of immunology (Baltimore, Md. : 1950). 2023 Sep 01;211(5):721-726