Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

L de Beaucoudrey, A Puel, O Filipe-Santos… - The Journal of …, 2008 - rupress.org
L de Beaucoudrey, A Puel, O Filipe-Santos, A Cobat, P Ghandil, M Chrabieh, J Feinberg…
The Journal of experimental medicine, 2008rupress.org
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) β, IL-1, IL-6, or IL-23
responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann …
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) β, 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-12Rβ1– 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.
rupress.org