通过调节RORγt转录活动,AIM2促进TH17细胞的分化
Jefferson Antônio Leite1,2,3, Luísa Menezes2, Eloisa Martins2,4
1Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
iScience
|October 23, 2023
概括
通过增强RORγt活性,AIM2蛋白促进了Th17细胞的分化. 它的缺失会损害Th17细胞的功能,并减少炎症性疾病,这表明AIM2是治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- AIM2 (在黑色素瘤中缺席2) 是一种干扰素诱导的DNA传感器,涉及天生的免疫力.
- 以前的研究表明AIM2在调节性T细胞 (Treg) 和毛囊性T细胞 (Tfh) 中的作用.
- 在T助手17 (Th17) 细胞分化中AIM2的功能以前是未知的.
研究的目的:
- 研究AIM2在Th17细胞分化中的作用.
- 阐明AIM2影响Th17细胞发育的分子机制.
- 评估AIM2对Th17细胞介导的炎症状况的影响.
主要方法:
- 在Th17细胞中AIM2表达的分析.
- 评估AIM2-缺乏细胞中的IL-17A产生和Th17相关蛋白水平 (RORγt,IL-1R1,IL-23R).
- 核定位和RORγt相互作用研究AIM2.
- 使用Rag1-/-小鼠进行体内研究,以评估大肠炎诱导.
主要成果:
- AIM2显著促进了Th17细胞的分化.
- 缺少AIM2导致IL-17A的产生减少,并减少了RORγt,IL-1R1和IL-23R的表达.
- 在Th17细胞的核中发现了AIM2,在那里它增强了RORγt与Il17a促进体的结合.
- 缺乏AIM2会损害Th17细胞分化,并减少体内结肠炎的发展.
结论:
- AIM2 作为 Th17 细胞转录编程的关键调节者.
- 在促进Th17细胞分化方面,AIM2的功能突显了其作为Th17细胞驱动的炎症性疾病的治疗点的潜力.
相关概念视频
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
B Cell Activation and Differentiation
1.7K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.7K
Master Transcription Regulators
6.9K
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...
6.9K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
T Cell Activation and Clonal Selection
764
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
764


