N-甘氨酸分支调节BTLA与PD-1相反,以限制因分支缺陷引起的T细胞过活性
Haik Mkhikian1, Raymond W Zhou2, Hayk Saryan2
1Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA.
Journal of immunology (Baltimore, Md. : 1950)
|September 13, 2024
概括
N-甘氨酸分支调节免疫细胞检查点. 分支增强PD-1表达,但降低BTLA表达,作为T细胞过活和炎症的关键控制.
科学领域:
- 免疫学 免疫学 免疫学
- 葡萄糖生物学 葡萄糖生物学
- 细胞生物学 细胞生物学
背景情况:
- N-甘氨酸分支通过调节细胞表面受体聚集和内细胞分裂来负面调节T和B细胞功能.
- 分支影响TCR,BCR和CTLA-4等关键受体,影响免疫细胞的激活和分化.
- 在调节检查点受体BTLA和PD-1中,N-甘氨酸分支的作用仍然未被探索.
研究的目的:
- 研究N-甘氨酸分支对B和T淋巴细胞减弱剂 (BTLA) 和编程细胞死亡蛋白1 (PD-1) 的细胞表面表达的影响.
- 了解N-甘氨酸分支如何影响这些检查点受体的内细胞分裂和细胞局部化.
- 确定改变BTLA和PD-1表达在具有不同N-甘氨酸分支水平的T细胞中的功能后果.
主要方法:
- 流细胞计,以评估T细胞和B细胞上BTLA和PD-1的细胞表面表达.
- 内细胞体检测量来量化受体内部化速率.
- 功能性检测测量T细胞激活和增殖,以应对改变的分支和受体表达.
主要成果:
- 通过减少其内细胞分裂,N-甘氨酸分支显著增加PD-1细胞表面表达.
- 相反,N-葡萄糖分支增强BTLA在T细胞和B细胞的内细胞分裂,导致表面表达较低.
- 由于缺陷分支导致的T细胞过活性被BTLA结合抵消,与增加的BTLA表面水平相关.
结论:
- N-甘氨酸分支通过对它们的内细胞分裂产生相反的影响,对BTLA和PD-1细胞表面水平进行差异调节.
- 在低分支的条件下,BTLA表达的增加起到补偿检查点的作用,以限制过度的T细胞过活和促炎反应.
- 这些发现揭示了一个新的机制,N-甘氨酸分支通过检查点受体调节微调免疫反应.
相关概念视频
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
T Cell Activation and Clonal Selection
688
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...
688
TGF - β Signaling Pathway
7.3K
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...
7.3K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
T Cell Types and Functions
961
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...
961
Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K


