CD137 ligand signaling induces human monocyte to dendritic cell differentiation

The ligand for CD137 (4‐1BB) is expressed on peripheral human monocytes and delivers a potent activating signal via reverse signaling. Here we show that treatment of monocytes with a recombinant CD137 protein that induces reverse signaling through CD137 ligand reduces typical macrophage characteristics such as phagocytosis, oxidative burst and CD14 expression; however, typical DC characteristics including endocytosis, costimulatory molecule expression and the ability to stimulate proliferation of naïve T cells are induced. CD137‐generated DC do not express DC‐SIGN, CD1a or IL‐12 and secrete less IL‐10 than classical DC. CD137‐generated DC are mature, and addition of LPS+IFN‐γ does not enhance their T‐cell‐stimulatory capacity. This indicates that CD137 as a sole factor is sufficient to induce development to mature DC, making stimulation of CD137 ligand the most simple protocol to generate mature DC. CD137‐generated DC are more potent in inducing T‐cell proliferation than classical DC. They inhibit development of Treg cells but induce T‐cell expression of perforin, IFN‐γ, IL‐13 and IL‐17. These data demonstrate that CD137 as a single factor is sufficient to induce differentiation of peripheral monocytes to mature inflammatory DC that have a more potent T‐cell‐stimulatory capacity than classical DC.