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ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1467774
This article is part of the Research Topic Community Series in the Role of CD1- and MR1-restricted T cells in Immunity and Disease: Volume II View all 17 articles
Eed-dependent histone modification orchestrates the iNKT cell developmental program alleviating liver injury
Provisionally accepted- 1 Hiroshima University, Hiroshima, Japan
- 2 Fukuoka University, Fukuoka, Fukuoka, Japan
- 3 Tokyo Women's Medical University, Shinjuku, Tōkyō, Japan
Polycomb repressive complex 2 (PRC2) is an evolutionarily conserved epigenetic modifier responsible for tri-methylation of lysine 27 on histone H3 (H3K27me3). Previous studies have linked PRC2 to invariant natural killer T (iNKT) cell development, but its physiological and precise role remained unclear. To address this, we conditionally deleted Eed, a core subunit of PRC2, in mouse T cells. The results showed that Eed-deficient mice exhibited a severe reduction in iNKT cell numbers, particularly NKT1 and NKT17 cells, while conventional T cells and NKT2 cells remained intact. Deletion of Eed disrupted iNKT cell differentiation, leading to increased cell death, which was accompanied by a severe reduction in H3K27me3 levels and abnormal expression of Zbtb16, Cdkn2a, and Cdkn1a. Interestingly, Eed-deficient mice were highly susceptible to acetaminophen-induced liver injury and inflammation in an iNKT cell-dependent manner, highlighting the critical role of Eed-mediated H3K27me3 marks in liver-resident iNKT cells. These findings provide further insight into the epigenetic orchestration of iNKT cell-specific transcriptional programs.
Keywords: iNKT, Eed, H3K27me3, PRC2, liver injury
Received: 20 Jul 2024; Accepted: 30 Aug 2024.
Copyright: © 2024 Guo, Ohki, Kawano, Kong, Ohno, Honda, Kanno and Yasuda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Tomoharu Yasuda, Hiroshima University, Hiroshima, Japan
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