From bench to bedside: targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases

Inflamm Res. 2023 Jun;72(6):1215-1235. doi: 10.1007/s00011-023-01742-y. Epub 2023 Jun 14.

Abstract

Background: Immune checkpoints negatively regulate immune response, thereby playing an important role in maintaining immune homeostasis. Substantial studies have confirmed that blockade or deficiency of immune checkpoint pathways contributes to the deterioration of autoimmune diseases. In this context, focusing on immune checkpoints might provide alternative strategies for the treatment of autoimmunity. Lymphocyte activation gene 3 (LAG3), as a member of immune checkpoint, is critical in regulating immune responses as manifested in multiple preclinical studies and clinical trials. Recent success of dual-blockade of LAG3 and programmed death-1 in melanoma also supports the notion that LAG3 is a crucial regulator in immune tolerance.

Methods: We wrote this review article by searching the PubMed, Web of Science and Google Scholar databases.

Conclusion: In this review, we summarize the molecular structure and the action mechanisms of LAG3. Additionally, we highlight its roles in diverse autoimmune diseases and discuss how the manipulation of the LAG3 pathway can serve as a promising therapeutic strategy as well as its specific mechanism with the aim of filling the gaps from bench to bedside.

Keywords: Autoimmune disease; Immune checkpoint; Immune regulation; LAG3; Therapy.

Publication types

  • Review

MeSH terms

  • Antigens, CD / genetics
  • Autoimmune Diseases* / therapy
  • Humans
  • Lymphocyte Activation
  • Lymphocyte Activation Gene 3 Protein
  • Neoplasms*

Substances

  • Lymphocyte Activation Gene 3 Protein
  • Antigens, CD