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From Bench to Bedside: Targeting Lymphocyte Activation Gene 3 As a Therapeutic Strategy for Autoimmune Diseases

Overview
Journal Inflamm Res
Date 2023 Jun 14
PMID 37314518
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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.

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References
1.
Cooper G, Stroehla B . The epidemiology of autoimmune diseases. Autoimmun Rev. 2003; 2(3):119-25. DOI: 10.1016/s1568-9972(03)00006-5. View

2.
Chamoto K, Al-Habsi M, Honjo T . Role of PD-1 in Immunity and Diseases. Curr Top Microbiol Immunol. 2017; 410:75-97. DOI: 10.1007/82_2017_67. View

3.
Schnell A, Bod L, Madi A, Kuchroo V . The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity. Cell Res. 2020; 30(4):285-299. PMC: 7118128. DOI: 10.1038/s41422-020-0277-x. View

4.
Dolladille C, Ederhy S, Sassier M, Cautela J, Thuny F, Cohen A . Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer. JAMA Oncol. 2020; 6(6):865-871. PMC: 7163782. DOI: 10.1001/jamaoncol.2020.0726. View

5.
Wherry E . T cell exhaustion. Nat Immunol. 2011; 12(6):492-9. DOI: 10.1038/ni.2035. View