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The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.

Original publication

DOI

10.1084/jem.20080321

Type

Journal article

Journal

J Exp Med

Publication Date

07/07/2008

Volume

205

Pages

1543 - 1550

Keywords

Cell Differentiation, Cytokines, Female, Genetic Diseases, Inborn, Humans, Interleukin-1 Receptor-Associated Kinases, Interleukin-17, Male, Mutation, Myeloid Differentiation Factor 88, Protein-Serine-Threonine Kinases, Quantitative Trait Loci, Receptors, Interleukin-12, Receptors, Transforming Growth Factor beta, STAT3 Transcription Factor, Signal Transduction, T-Lymphocytes, Helper-Inducer