Identification of IL-17-producing FOXP3+ regulatory T cells in humans
By K. Voo, Yu Wang, F. R. Santori, C. Boggiano, Yi-hong Wang, K. Arima, L. Bover, S. Hanabuchi, Jahan S Khalili, E. Marinova and 3 more. Proceedings of the National Academy of Sciences of the United States of America, 2009
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IL-17–producing CD4+ T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-β, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORγt. The maintenance, expansion, and further differentiation of the committed Th17 cells depend on IL-1β and IL-23. IL-17 was originally found produced by circulating human CD45RO+ memory T cells. A recent study found that human Th17 memory cells selectively express high levels of CCR6. In this study, we report that human peripheral blood and lymphoid tissue contain a significant number of CD4+FOXP3+ T cells that express CCR6 and have the capacity to produce IL-17 upon activation. These cells coexpress FOXP3 and RORγt transcription factors. The CD4+FOXP3+CCR6+ IL-17–producing cells strongly inhibit the proliferation of CD4+ responder T cells. CD4+CD25high-derived T-cell clones express FOXP3, RORγt, and IL-17 and maintain their suppressive function via a cell-cell contact mechanism. We further show that human CD4+FOXP3+CCR6− regulatory T (Treg) cells differentiate into IL-17 producer cells upon T-cell receptor stimulation in the presence of IL-1β, IL-2, IL-21, IL-23, and human serum. This, together with the finding that human thymus does not contain IL-17–producing Treg cells, suggests that the IL-17+FOXP3+ Treg cells are generated in the periphery. IL-17–producing Treg cells may play critical roles in antimicrobial defense, while controlling autoimmunity and inflammation.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/4cdd6f60cba2a9436dea2e24ead089f725836e1c
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In Immunology
Citations in the corpus
- Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis. (2015, background): “Several studies have characterized the phenotype and function of CD4+ TH cells from human peripheral blood and tonsils, including TH17, Treg, and CXCR5 + TFH cells (Lim et al., 2008; Schmitt et al., 2014; Voo et al., 2009).”
- Plasticity of CD4+ T cell lineage differentiation. (2009, background): “Circulating human Foxp3IL-17 T cells have in vitro suppressive activity (Beriou et al., 2009; Voo et al., 2009), but it is not yet known whether they have the functions of conventional Th17 cells.”