Department of Microbiology, New York University School of Medicine, New York, NY 10016;
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;
J Immunol. 2014 Aug 1;193(3):1047-54. doi: 10.4049/jimmunol.1302936. Epub 2014 Jun 23.
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.
一小部分人类调节性 T 细胞（Tregs）分泌白介素-17（IL-17），因此类似于 Th17 效应细胞。IL-17（+）Tregs 如何从幼稚前体分化仍不清楚。在这项研究中，我们表明，在 IL-2、IL-1β、TGF-β 和 IL-23 的存在下，IL-17 产生的 T 细胞可以从 CCR6（+）幼稚 T 细胞前体分化而来。CCR6（+）幼稚 T 细胞存在于成人外周血和脐带血中，以及传统的 T 幼稚和 FOXP3（+）幼稚 Treg 亚群中。源自 CCR6（+）幼稚 Tregs 的 IL-17（+）细胞（称为 IL-17（+）Tregs）表达 FOXP3，但不表达 HELIOS，另一种与 Treg 相关的转录因子，这些细胞具有抑制能力和类似于记忆 Treg 的表面表型。值得注意的是，在一部分 HIV（+）受试者中，与经典 Th17 和 Treg 亚群相比，IL-17（+）Treg 亚群优先减少，这表明在疾病过程中该亚群受到了特定的干扰。我们的发现表明，CCR6（+）幼稚前体中存在一个预先确定的储备库，可补充分泌白介素-17 的细胞，这可能对平衡 HIV 感染期间和潜在其他炎症性疾病期间受到干扰的 Th17 和 IL-17（+）Treg 亚群具有重要意义。
