TNFR2 signalling in inflammatory diseases

IF 4.5 2区医学 Q1 RHEUMATOLOGY

Best Practice & Research in Clinical Rheumatology Pub Date : 2024-05-01 DOI:10.1016/j.berh.2024.101941

引用次数: 0

Abstract

TNF signals via two receptors, TNFR1 and TNFR2, which play contrasting roles in immunity. Most of the pro-inflammatory effects of TNF are mediated by TNFR1, whereas TNFR2 is mainly involved in immune homeostasis and tissue healing, but also contributes to tumour progression. However, all currently available anti-TNF biologics inhibit signalling via both receptors and there is increasing interest in the development of selective inhibitors; TNFR1 inhibitors for autoimmune disease and TNFR2 inhibitors for cancer. It is hypothesised that selective inhibition of TNFR1 in autoimmune disease would alleviate inflammation and promote homeostasis by allowing TNFR2 signalling to proceed unimpeded. Validation of this concept would pave the way for the development and testing of TNF specific antagonists. Another therapeutic approach being explored is the use of TNFR2 specific agonists, which could be administered alone or in combination with a TNFR1 antagonist.

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炎症性疾病中的 TNFR2 信号。

TNF 通过 TNFR1 和 TNFR2 两种受体发出信号，它们在免疫中发挥着截然不同的作用。TNF 的大多数促炎作用都是由 TNFR1 介导的，而 TNFR2 则主要参与免疫平衡和组织愈合，但也有助于肿瘤进展。然而，目前所有可用的抗 TNF 生物制剂都会抑制通过这两种受体发出的信号，人们对开发选择性抑制剂的兴趣与日俱增；TNFR1 抑制剂用于治疗自身免疫性疾病，TNFR2 抑制剂用于治疗癌症。据推测，在自身免疫性疾病中选择性抑制 TNFR1 可使 TNFR2 信号传递畅通无阻，从而缓解炎症并促进体内平衡。这一概念的验证将为开发和测试 TNF 特异性拮抗剂铺平道路。目前正在探索的另一种治疗方法是使用 TNFR2 特异性激动剂，这种激动剂可以单独使用，也可以与 TNFR1 拮抗剂联合使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Best Practice & Research in Clinical Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

0.00%

发文量

审稿时长

27 days

期刊介绍： Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions. Best Practice & Research: Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science. The series provides a continuous update of current clinical practice. It is a topical serial publication that covers the spectrum of musculoskeletal conditions in a 4-year cycle. Each topic-based issue contains around 200 pages of practical, evidence-based review articles, which integrate the results from the latest original research with current clinical practice and thinking to provide a continuous update. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. The review articles seek to address the clinical issues of diagnosis, treatment and patient management. Management is described in practical terms so that it can be applied to the individual patient. The serial is aimed at the physician in both practice and training.