Lymphocyte activation gene-3 (LAG-3) regulatory T cells: An evolving biomarker for treatment response in autoimmune diseases

Regulatory T cells (Tregs) comprise a CD4+CD25+Foxp3+ T cell subset for maintaining immune tolerance, and their deficits and/or dysfunction are observed in autoimmune diseases. The lymphocyte activation gene 3 (LAG-3, also known as CD223), which is an immunoglobulin superfamily member expressed on peripheral immune cells, is recognized as an inhibitory regulator of Tregs. LAG-3+ T cells represent a novel protective Tregs subset that produces interleukin-10. Alterations in LAG-3+ Tregs have been reported in several autoimmune diseases, suggesting their potential pathogenic role. Recent studies have indicated that LAG-3+ Tregs may be associated not only with immunopathology but also with response to therapy in several autoimmune and autoinflammatory diseases, such as rheumatoid arthritis, psoriasis, psoriatic arthritis and others. We present a review of Tregs phenotypes and functions, with a focus on LAG-3+ Tregs, and discuss their potential role as biomarkers for treatment response in autoimmune diseases.