组织素脱乙酶HDAC1控制树突细胞的发育和抗瘤免疫力
Cristiano De Sá Fernandes1, Philipp Novoszel1, Tommaso Gastaldi1
1Center for Cancer Research, Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria.
Cell reports
|June 3, 2024
概括
基斯脱乙酶1 (HDAC1) 对于树突细胞 (DC) 发育和抗瘤免疫是至关重要的. 它的缺失通过促进特定的DC子集和T细胞免疫力来增强抗瘤反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 树突细胞 (DCs) 是关键的免疫调节体,具有来自祖细胞的多样化子集.
- 染色质修饰的作用,特别是基因素脱乙烯化,在DC子集的发展仍然在很大程度上未被描述.
研究的目的:
- 为了研究基因组脱乙酶1 (HDAC1) 和HDAC2对树突细胞发育和功能的影响.
- 阐明HDAC1调节DC子集分化和抗瘤免疫的分子机制.
主要方法:
- 在小鼠造血原体和CD11c表达细胞中,HDAC1或HDAC2的遗传删除.
- 在人类造血细胞中,HDAC1被击败.
- 多基因组学分析 (包括转录基因组学和表观基因组学) 以评估基因表达和染色质可访问性.
- 评估DC子群种群,T辅助细胞反应和CD8+T细胞招募.
主要成果:
- HDAC1,但不是HDAC2,对于等离子体细胞直流体 (pDC) 和某些常规直流体 (cDC2) 的发展至关重要.
- HDAC1调节了对cDC2发育至关重要的关键转录因子 (IRF4,IRF8,SPIB) 的表达和可访问性.
- 失去HDAC1会重新编程DC来增强抗瘤免疫力,其特征是cDC1成熟度增加,IL-12产生,CD8+T细胞招募.
结论:
- 由HDAC1控制的基因组乙化,在调节树突细胞发育和分化方面发挥着至关重要的作用.
- 在DC中准HDAC1可能代表一种新的治疗策略,用于提高免疫瘤学中的抗瘤免疫力.
关键词:
在ATAC-seqq中使用.CP: 癌症 癌症 癌症CP: 免疫学 免疫学切断和运行 切断和运行在HDAC的基础上,HDAC是在 IRF 基础上,IRF 已经成为了 IRF.cDC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC1DC2DC1DC1DC2DC2DC2DC2DC2DC3DC4cDC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2DC2树突细胞的树突细胞.表观遗传学是指表观遗传学.在pDCDC中,pDC是瘤免疫力 免疫力相关概念视频
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Histone Modification
13.2K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.2K
Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K


