TNF biology, pathogenic mechanisms and emerging therapeutic strategies

被引：1249

作者：

Kalliolias, George D. ^{[1
]}

Ivashkiv, Lionel B.

机构：

[1] Hosp Special Surg, Arthrit & Tissue Degenerat Program, New York, NY 10021 USA

来源：

NATURE REVIEWS RHEUMATOLOGY | 2016年 / 12卷 / 01期

关键词：

TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FIBROBLAST-LIKE SYNOVIOCYTES; FACTOR-ALPHA NEUTRALIZATION; DNA METHYLOME SIGNATURE; E3 LIGASE ITCH; RHEUMATOID-ARTHRITIS; SIGNALING PATHWAYS; UBIQUITIN CHAINS; GENE-EXPRESSION;

D O I：

10.1038/nrrheum.2015.169

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

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.

引用

页码：49 / 62

页数：14

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