title: Differentiation of IL-17-producing effector and regulatory human T cells from lineage-committed naive precursors.
abstract: A subset of human regulatory T cells (Tregs) secretes IL-17 and thus resembles Th17 effector cells. How IL-17(+) Tregs differentiate from naive precursors remains unclear. In this study, we show that IL-17-producing T cells can differentiate from CCR6(+) naive T cell precursors in the presence of IL-2, IL-1β, TGF-β, and IL-23. CCR6(+) naive T cells are present in adult peripheral and umbilical cord blood and in both conventional T naive and FOXP3(+) naive Treg subsets. IL-17(+) cells derived from CCR6(+) naive Tregs (referred to as IL-17(+) Tregs) express FOXP3 but not HELIOS, another Treg-associated transcription factor, and these cells display suppressor capacity and a surface phenotype resembling memory Tregs. Remarkably, the IL-17(+) Treg compartment was preferentially reduced relative to the canonical Th17 and Treg compartments in a subset of HIV(+) subjects, suggesting a specific perturbation of this subset during the course of disease. Our findings that CCR6(+) naive precursors contain a predetermined reservoir to replenish IL-17-secreting cells may have implications in balancing the Th17 and IL-17(+) Treg compartments that are perturbed during HIV infection and potentially in other inflammatory diseases.
authors: Department of Microbiology, New York University School of Medicine, New York, NY 10016;
authors: Frances
authors: F
authors: Mercer
authors: Department of Pediatrics, New York University School of Medicine, New York, NY 10016; Division of Infectious Diseases, New York University School of Medicine, New York, NY 10016;
authors: Alka
authors: A
authors: Khaitan
authors: Department of Microbiology, New York University School of Medicine, New York, NY 10016;
authors: Lina
authors: L
authors: Kozhaya
authors: Division of Infectious Diseases, New York University School of Medicine, New York, NY 10016; Department of Medicine, New York University School of Medicine, New York, NY 10016; and.
authors: Judith A
authors: JA
authors: Aberg
authors: Department of Microbiology, New York University School of Medicine, New York, NY 10016; Department of Medicine, New York University School of Medicine, New York, NY 10016; and Department of Pathology, New York University School of Medicine, New York, NY 10016 Derya@mac.com.
authors: Derya
authors: D
authors: Unutmaz
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007231:Infant, Newborn / Q000097:blood; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis* / Q000378:metabolism; D054399:Receptors, CCR6 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019562:Viral Load
chemical_list: C106311:CCR6 protein, human; D020381:Interleukin-17; D011498:Protein Precursors; D054399:Receptors, CCR6