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

• Published in: Journal of autoimmunity 2020-08, Vol.112, p.102499-102499, Article 102499
• Main Authors: Wong, Hiu Yi, Schwarz, Herbert
• Format: Article
• Language: English
• Subjects: Autoimmunity; CD137; CD137L; Immunotherapy; Soluble CD137
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2020.102499

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. •The cytokine receptor CD137 (TNFRSF9, 4-1BB) potently costimulates antigen-specific T cells, and polarizes them towards a Th1/Tc1 response.•CD137 agonists enhance autoimmune diseases that are caused by a Th1/Tc1 response while ameliorating those that are caused by a Th2 or Th17 response.•Interference with CD137 – CD137L interaction skews an immune response away from a cellular Th1/Tc1 response.•As CD137 identifies T cells that have encountered antigen, their depletion may provide a novel approach for immunotherapy of autoimmune diseases.