表观遗传学
炎症
肿瘤坏死因子α
医学
平衡
坏死性下垂
机制(生物学)
免疫学
信号转导
生物
疾病
生物信息学
计算生物学
神经科学
发病机制
细胞生物学
基因
细胞凋亡
遗传学
程序性细胞死亡
哲学
病理
认识论
作者
George D. Kalliolias,Lionel B. Ivashkiv
标识
DOI:10.1038/nrrheum.2015.169
摘要
TNF is a pleiotropic cytokine with important functions in homeostasis and disease pathogenesis. Recent discoveries have provided insights into TNF biology that introduce new concepts for the development of therapeutics for TNF-mediated diseases. The model of TNF receptor signalling has been extended to include linear ubiquitination and the formation of distinct signalling complexes that are linked with different functional outcomes, such as inflammation, apoptosis and necroptosis. Our understanding of TNF-induced gene expression has been enriched by the discovery of epigenetic mechanisms and concepts related to cellular priming, tolerization and induction of 'short-term transcriptional memory'. Identification of distinct homeostatic or pathogenic TNF-induced signalling pathways has introduced the concept of selectively inhibiting the deleterious effects of TNF while preserving its homeostatic bioactivities for therapeutic purposes. In this Review, we present molecular mechanisms underlying the roles of TNF in homeostasis and inflammatory disease pathogenesis, and discuss novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases.
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