Nck1通过AKT通路调节人体调节性T细胞的体外发育
Aussanee Nuiyen1, Donruedee Sanguansermsri1, Jarun Sayasathid2
1Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
Clinical and experimental immunology
|February 18, 2025
概括
氨酸激酶1 (Nck1) 的非催化区域对于调节性T细胞 (Treg) 发育至关重要. 在人体胸细胞中抑制Nck1显著降低了Treg数量,并改变了涉及它们分化的关键信号通路.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- T细胞受体 (TCR) 信号传递决定了胸细胞的分化.
- 调节性T细胞 (Tregs) 对于免疫平衡至关重要,通过TCR与自我抗原的相互作用而发展.
- 叉头盒P3 (FoxP3) 是Treg谱系承诺的一个关键转录因子.
研究的目的:
- 调查Nck1在体外发育和分化中的人类胸细胞到Tregs.的作用.
- 阐明Nck1影响Treg发育的分子机制.
主要方法:
- 人类胸细胞被shRNA感染,以击败Nck1的表达.
- 在14天的时间里,Nck1沉默的胸细胞与髓状树突细胞 (mDCs) 和胸膜上皮细胞共同培养.
- 使用流式细胞计和西式斑点测试来评估Treg数量,FoxP3表达和蛋白质酸化 (AKT,FoxO1).
主要成果:
- Nck1的淘汰导致FoxP3+Tregs的数量显著下降.
- 在Nck1沉默的胸细胞中观察到AKT和FoxO1的酸化减少.
- Nck1沉默与FoxO1.1的核定位减少有关.
结论:
- Nck1在人类调节性T细胞的发育中起着关键作用.
- 通过对AKT/FoxO1通路的调制,Nck1信号影响Treg分化.
- 这些发现凸显了Nck1作为调节Treg种群的潜在目标.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
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...
2.0K
Inhibition of Cdk Activity
4.6K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
TGF - β Signaling Pathway
7.2K
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...
7.2K


