TOXは,CD8+ T細胞の枯渇を転写的におよび表遺伝的にプログラムする
Omar Khan1,2,3,4, Josephine R Giles1,2,3, Sierra McDonald5,6,7
1Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|June 18, 2019
まとめ
転写因子TOXは,がんおよび慢性感染症において重要な標的である,枯渇したCD8+ T (Tex) 細胞の発達に不可欠である. その欠如はTex細胞の形成を阻害し,Tex細胞枯渇の重要なレギュラーとしてTOXを強調する.
科学分野:
- 免疫学
- 分子生物学
- 細胞生物学
背景:
- 枯渇したCD8+T (Tex) 細胞は,エフェクタ機能の障害と独特の表遺伝子および転写プロファイルを示します.
- Tex細胞は,慢性感染症やがんにおけるチェックポイントブロックのような免疫療法の重要な標的です.
- Tex細胞の転写および表遺伝的発達を駆動するメカニズムは十分に理解されていません.
研究 の 目的:
- Tex細胞発達の重要なレギュレータを特定する.
- Tex細胞フェノタイプを確立するにおける転写因子の役割を解明する.
主な方法:
- マウスモデルにおけるCD8+ T細胞サブセット (Tex,Teff,Tmem) の分析
- Tex細胞の発達におけるHMGボックス転写因子TOXの役割を調査した.
- Tex細胞のプログラミングを特徴づけるために分子と表遺伝子解析を用いた.
主要な成果:
- マウスにおけるTex細胞形成に不可欠な中央調節剤としてTOXを特定した.
- TOXはカルシヌーリン/NFAT2によって誘発され,Tex細胞におけるカルシヌーリンに独立した継続的なフィードフォワードループで作用する.
- TOXは,Tex細胞のコミットメントに特異なトランスクリプションおよび表遺伝的プログラムをオーケストラします.
結論:
- TOXはTex細胞の運命を決定する重要な要素であり,絶え間ない刺激を疲労に変換します.
- TOXの役割を理解することで,治療上の利点のためにTex細胞をターゲットにするための洞察が得られます.
関連する概念動画
01:46Epigenetic Regulation
33.5K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.5K
01:37Epigenetic Regulation
3.7K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.7K
01:10Transcription
155.8K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
155.8K
02:16Transcription Factors
82.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.3K
02:23Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
02:35Transcription Elongation Factors
13.5K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.5K