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We are analyzing https://www.nature.com/articles/ni.1610.

Title:
The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt | Nature Immunology
Description:
TH-17 cells are interleukin 17 (IL-17)–secreting CD4+ T helper cells involved in autoimmune disease and mucosal immunity. In naive CD4+ T cells from mice, IL-17 is expressed in response to a combination of IL-6 or IL-21 and transforming growth factor-β (TGF-β) and requires induction of the nuclear receptor RORγt. It has been suggested that the differentiation of human TH-17 cells is independent of TGF-β and thus differs fundamentally from that in mice. We show here that TGF-β, IL-1β and IL-6, IL-21 or IL-23 in serum-free conditions were necessary and sufficient to induce IL-17 expression in naive human CD4+ T cells from cord blood. TGF-β upregulated RORγt expression but simultaneously inhibited its ability to induce IL-17 expression. Inflammatory cytokines relieved this inhibition and increased RORγt-directed IL-17 expression. Other gene products detected in TH-17 cells after RORγt induction included the chemokine receptor CCR6, the IL-23 receptor, IL-17F and IL-26. Our studies identify RORγt as having a central function in the differentiation of human TH-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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  • Science
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Keywords {🔍}

pubmed, article, google, scholar, cas, cells, nature, human, immunol, interleukin, central, receptor, differentiation, cell, york, nat, cytokine, access, transforming, growth, littman, helper, tgfβ, med, content, rorγt, inflammatory, ilr, production, function, factorβ, induction, disease, immunity, cookies, nuclear, dan, expression, medicine, privacy, immunology, autoimmune, naive, mice, gene, exp, proinflammatory, usa, institute, data,

Topics {✒️}

cancer research institute nature portfolio permissions reprints privacy policy transforming growth factor-β–dependent advertising social media central nervous system-infiltrating transforming growth factor-β transforming growth factor-beta author information authors nature 445 nature 441 nature 448 nature modular tyrosine-based motifs t-cell receptor diversity data protection t-cell receptor stimulation author correspondence nf-κb signal pathway bearing ccr2+ccr5− phenotype personal data springerlink instant access development nuclear receptor rorγt serum-free conditions permissions il-23-mediated il-17 production 17 cell–mediated pathology naive human cd4+foxp3− cell receptor ligation promote interleukin-17 production inflammatory cytokines relieved cell differentiation mediated similar cytokine pathways privacy th17 cell differentiation article manel require tgf-β inflammatory bowel disease terminal ileum mediated stat3-dependent manner studies identify rorγt chemokine receptor ccr6 receptor-activated monocytes induce il-17 expression il-23/th17 axis il-26+ th17 intermediates cytokine receptor subunit

Schema {🗺️}

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      headline:The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt
      description:TH-17 cells are interleukin 17 (IL-17)–secreting CD4+ T helper cells involved in autoimmune disease and mucosal immunity. In naive CD4+ T cells from mice, IL-17 is expressed in response to a combination of IL-6 or IL-21 and transforming growth factor-β (TGF-β) and requires induction of the nuclear receptor RORγt. It has been suggested that the differentiation of human TH-17 cells is independent of TGF-β and thus differs fundamentally from that in mice. We show here that TGF-β, IL-1β and IL-6, IL-21 or IL-23 in serum-free conditions were necessary and sufficient to induce IL-17 expression in naive human CD4+ T cells from cord blood. TGF-β upregulated RORγt expression but simultaneously inhibited its ability to induce IL-17 expression. Inflammatory cytokines relieved this inhibition and increased RORγt-directed IL-17 expression. Other gene products detected in TH-17 cells after RORγt induction included the chemokine receptor CCR6, the IL-23 receptor, IL-17F and IL-26. Our studies identify RORγt as having a central function in the differentiation of human TH-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
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