Early Growth Response Gene 2-Expressing CD4LAG3 Regulatory T Cells: The Therapeutic Potential for Treating Autoimmune Diseases.

Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4CD25 Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor is well known as a master regulatory gene for the development and function of CD4CD25 Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells. Lymphocyte activation gene 3 (LAG3) and CD49b are reliable cell surface markers for Tr1 cells. CD4CD25LAG3 Tregs (LAG3 Tregs) develop in the periphery and produce a large amount of IL-10. LAG3 Tregs characteristically express the early growth response gene 2 (), a zinc-finger transcription factor, and exhibit its suppressive activity in a Foxp3-independent manner. Although was known to be essential for hindbrain development and myelination of the peripheral nervous system, recent studies revealed that plays vital roles in the induction of T cell anergy and also the suppressive activities of LAG3 Tregs. Intriguingly, forced expression of converts naive CD4 T cells into IL-10-producing Tregs that highly express LAG3. Among the four gene family members, is thought to compensate for the function of . Recently, we reported that LAG3 Tregs suppress humoral immune responses transforming growth factor β3 production in an Egr2- and Egr3-dependent manner. In this review, we focus on the role of in Tregs and also discuss its therapeutic potential for the treatment of autoimmune diseases.