Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells

CD4(+) T helper cell differentiation is essential for mounting robust immune responses without compromising unresponsiveness toward self-tissue. Here, we show that different subsets of myeloid cells isolated from human peripheral blood modulate TGF-beta-dependent CD4+ T-cell developmental programs ex vivo. Human CD14(+)HLA-DR-/low myeloid-derived suppressor cells (MDSCs) induce Foxp3(+) regulatory T cells, whereas CD14(+)HLA-DR+ monocytes promote generation of IL-17-secreting RORc(+) Th17 cells when cocultured with naive CD4(+) T cells. More importantly, not only do these 2 subsets modulate the de novo induction of Tregs and Th17 cells from CD4(+) T cells, but MDSCs also catalyze the transdifferentiation of Foxp3(+) regulatory T cells from monocyte-induced Th17 cells. The mechanism of such Th17 plasticity is dependent on MDSC-derived TGF-beta and retinoic acid. Our results identify a previously unknown feature of the different subsets of CD14(+) myeloid cells namely their pivotal role in immune response regulation and plasticity of CD4(+) T helper cells. We propose that different subsets of myeloid cells in humans can orchestrate the differentiation of naive CD4(+) T cells into effector/regulatory T-cell subsets. The balance between these 2 subsets can impact the outcome of immune reaction from inflammation to tolerance. (Blood. 2011;117(24):6532-6541)