CD137 / CD137 ligand signalling regulates the immune balance: A potential target for novel immunotherapy of autoimmune diseases

J Autoimmun. 2020 Aug:112:102499. doi: 10.1016/j.jaut.2020.102499. Epub 2020 Jun 4.

Abstract

CD137 (TNFRSF9, 4-1BB) is a potent co-stimulatory molecule of the tumour necrosis factor receptor superfamily (TNFRSF) that is expressed by activated T cells. CD137/CD137 ligand (CD137L) signalling primarily induces a potent cell-mediated immune response, while signalling of cell surface-expressed CD137L into antigen presenting cells enhances their activation, differentiation and migratory capacity. Studies have shown that bidirectional CD137/CD137L signalling plays an important role in the pathogenesis of autoimmune diseases. This review discusses the mechanisms how CD137/CD137L signalling contributes to immune deviation of helper T cell pathways in various murine models, and the potential of developing immunotherapies targeting CD137/CD137L signalling for the treatment of autoimmune diseases.

Keywords: Autoimmunity; CD137; CD137L; Immunotherapy; Soluble CD137.

Publication types

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

MeSH terms

  • 4-1BB Ligand / antagonists & inhibitors
  • 4-1BB Ligand / metabolism*
  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Mice
  • Molecular Targeted Therapy / methods
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / antagonists & inhibitors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*

Substances

  • 4-1BB Ligand
  • Immunologic Factors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9