title: Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells.
abstract: 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-β-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-β 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.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Hoechst
authors.forename: Jaba
authors.initials: J
authors.lastname: Gamrekelashvili
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Korangy
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D046228:Microarray Analysis; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D053773:Transforming Growth Factor beta1; D014212:Tretinoin