[Toward therapeutic application of IL-10-producing regulatory T cells]

IL-10 is an anti-inflammatory cytokine with an important role in preventing inflammatory and autoimmune responses. IL-10 is also important for suppressive function of inducible regulatory T (iTreg) cells, several types of which were reported in succession. Type1 regulatory T (Tr1) cell is a representative of IL-10-prroducing regulatory T cells. Although specific surface markers or origin of Tr1 cells have not fully been clarified yet, IL-27 was recently reported to induce IL-10 production in T cells and be an inducer of Tr1 cells. We previously reported that CD4(+)CD25(-)lymphocyte activation gene (LAG-3)(+) Treg (LAG3(+) Treg) is one of the peripherally inducible Tregs and functions as an immune-regulator through IL-10 production. We found that the expression level of Egr-2, a transcription factor required for T cell anergy induction, is elevated in LAG3(+) Treg and that forced expression of Egr-2 induces LAG-3 expression and IL-10 production. Egr-2 has been suggested to be a key player of regulatory function in LAG3(+) Treg. In this study, we review Tr1 cells and the mechanism of IL-10 induction by IL-27 in T cells. Also, we introduce LAG3(+) Treg and discuss the therapeutic potential of these regulatory T cells.