一个轴突-T细胞反循环增强了炎症和轴突退化
Tingting Liu1, Huanhuan Wang2, Daniel Y Kutsovsky3
1Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA; IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
Cell reports
|February 4, 2024
概括
交感轴突通常会抑制皮肤炎症. 然而,强烈的炎症会对这些轴突造成T细胞介导的损伤,消除这种抑制,并产生炎症和神经退行的有害反循环.
科学领域:
- 神经免疫学 神经免疫学
- 神经炎症是一种神经炎症.
- 周围神经系统生物学 周围神经系统生物学
背景情况:
- 在许多疾病中,炎症和神经退行症是密切相关的.
- 在这种关系中区分原因和结果是具有挑战性的.
- 轴突损伤是神经退行的一个标志,但其与炎症的关系需要澄清.
研究的目的:
- 解开炎症和轴突损伤在神经退行过程中的作用.
- 为了研究同情轴突和皮肤中的免疫细胞之间的双向通信.
- 阐明导致炎症的轴突退化背后的机制.
主要方法:
- 在小鼠皮肤中模拟炎症损伤,使用Toll-like受体7激活剂imiquimod.
- 独立地阻断细胞毒性T细胞功能和轴突退化.
- 评估上腺素和β2上腺素受体在交感轴突与免疫细胞相互作用中的作用.
- 调查轴突损失中的Sarm1-依赖性途径.
主要成果:
- 交感轴突释放诺上腺素,通过β2上腺素受体抑制γδT细胞的激活.
- 炎症刺激导致免疫抑制性交感轴突的渐进性,γδ T 细胞介导的,Sarm1 依存的损失.
- 这种轴突损失消除了T细胞的车,创造了增加炎症和轴突损伤的积极反循环.
结论:
- 交感神经系统在调节皮肤炎症方面发挥着至关重要的作用.
- 炎症可以通过特定的免疫路径直接导致神经退行 (轴突损伤).
- 炎症和轴突损伤之间的正反循环可以加剧神经炎症状况.
相关概念视频
01:07Cell Signaling Feedback Loops
6.3K
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
6.3K
01:15Neurogenesis and Regeneration of Nervous Tissue
792
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
792
03:14Notch Signaling Pathway
4.3K
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...
4.3K
01:24T 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
01:21Neurons: The Axon
3.5K
Axons are long, cytoplasmic processes of nerve cells capable of propagating electrical impulses known as action potentials. The cytoplasm or axoplasm of an axon contains neurofibrils, neurotubules, small vesicles, lysosomes, mitochondria, and various enzymes, all encased within the axolemma, the plasma membrane of the axon.
The axon attaches to the cell body at a cone-shaped elevation called the axon hillock. The initial part of the axon, closest to the hillock, is known as the initial segment....
The axon attaches to the cell body at a cone-shaped elevation called the axon hillock. The initial part of the axon, closest to the hillock, is known as the initial segment....
3.5K
01:25Nervous Tissue: Myelin
2.6K
The myelin sheath is a multilayered lipid and protein covering that insulates the axon of a neuron, enhancing the speed of nerve impulse conduction. Axons without this sheath are referred to as unmyelinated. Two types of neuroglia, Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS) are responsible for producing myelin sheaths.
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
Schwann cells begin to form myelin sheaths around axons during fetal development. They wrap around a small...
2.6K