Death receptor 3 signaling enhances proliferation of human regulatory T cells

Exploiting regulatory T cells (Tregs) to control aberrant immune reactions is a promising therapeutic approach, but is hampered by their relative paucity. In mice, activation of death receptor 3 ( DR 3), a member of the TNF ‐receptor superfamily ( TNFRSF ), increases Treg frequency and efficiently controls exuberant immune activation. For human Tregs, neither DR 3 expression nor potential functions have been described. Here, we show that human Tregs express DR 3 and demonstrate DR 3‐mediated activation of p38, ERK , and NF κB. DR 3 stimulation enhances Treg expansion ex vivo while retaining their suppressive capacity. In summary, our results establish a functional role for DR 3 signaling in human Tregs and could potentially help to tailor Treg‐based therapies.