La Jolla Institute for Allergy and Immunology, Division of Immune Regulation, 9420 Athena Circle, La Jolla, CA 92037, United States.
La Jolla Institute for Allergy and Immunology, Division of Immune Regulation, 9420 Athena Circle, La Jolla, CA 92037, United States.
Cytokine. 2018 Jan;101:14-18. doi: 10.1016/j.cyto.2016.08.003. Epub 2016 Aug 13.
TNF (tumor necrosis factor) is both a pro-inflammatory and anti-inflammatory cytokine that is central to the development of autoimmune disease, cancer, and protection against infectious pathogens. As well as a myriad other activities, TNF can be a product of T cells and can act on T cells. Here we review old and new data on the importance of TNF produced by T cells and how TNF signaling via TNFR2 may directly impact alternate aspects of T cell biology. TNF can promote the activation and proliferation of naïve and effector T cells, but also can induce apoptosis of highly activated effector T cells, further determining the size of the pathogenic or protective conventional T cell pool. Moreover, TNF can have divergent effects on regulatory T cells. It can both downregulate their suppressive capacity, but also contribute in other instances to their development or accumulation. Biologics that block TNF or stimulate TNFR2 therefore have the potential to strongly modulate the balance between effector T cells and Treg cells which could impact disease in both positive and negative manners.
肿瘤坏死因子(TNF)既是一种促炎细胞因子,也是一种抗炎细胞因子,它是自身免疫性疾病、癌症和抗感染病原体保护的核心。除了无数其他的活动外,TNF 可以是 T 细胞的产物,并可以作用于 T 细胞。在这里,我们回顾了 T 细胞产生的 TNF 的重要性的新旧数据,以及 TNFR2 介导的 TNF 信号如何直接影响 T 细胞生物学的其他方面。TNF 可以促进幼稚和效应 T 细胞的激活和增殖,但也可以诱导高度激活的效应 T 细胞凋亡,进一步决定致病性或保护性常规 T 细胞池的大小。此外,TNF 对调节性 T 细胞也有不同的影响。它既能下调其抑制能力,也能在其他情况下促进其发育或积累。因此,阻断 TNF 或刺激 TNFR2 的生物制剂有可能强烈调节效应 T 细胞和 Treg 细胞之间的平衡,这可能以积极和消极的方式影响疾病。
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