Research ArticleAUTOIMMUNITY

LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes

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Science Immunology  31 Mar 2017:
Vol. 2, Issue 9, eaah4569
DOI: 10.1126/sciimmunol.aah4569

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Regulating the regulators

Inhibitory receptors on T cells, including lymphocyte activation gene 3 (LAG3), serve as brakes that limit immune-mediated damage to the host. LAG3 is expressed by exhausted conventional T cells in the tumor microenvironment and has emerged as a key target for tumor immunotherapy. The role of LAG3 in regulatory T cells (Tregs) has remained unclear. Using a mouse model of autoimmune diabetes, Zhang et al. report that Treg-specific deletion of LAG3 led to enhanced Treg proliferation and reduced the incidence of type 1 diabetes. Their studies highlight the cell-type dependence and context specificity of the role of LAG3 and call for a more holistic assessment of the functions of inhibitory receptors that emerge as targets for tumor immunotherapies.