TNFR2 signalling in inflammatory diseases

Best Pract Res Clin Rheumatol. 2024 May;38(2):101941. doi: 10.1016/j.berh.2024.101941. Epub 2024 Mar 27.

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.

Keywords: Autoimmunity; Inflammation; Rheumatoid arthritis; TNF; TNF receptors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / immunology
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Receptors, Tumor Necrosis Factor, Type I* / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor, Type II*
  • Signal Transduction* / drug effects
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Receptors, Tumor Necrosis Factor, Type II
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha