Beaucoudrey, L.Puel, A.Filipe-Santos, O.Cobat, A.Ghandil, P.Chrabieh, M.Feinberg, J.Bernuth, H.Samarina, A.Jannière, L.Fieschi, C.Stéphan, J.Boileau, C.Lyonnet, S.Jondeau, G.Cormier-Daire, V.Merrer, M.Hoarau, C.Lebranchu, Y.Lortholary, O.Chandesris, M.Tron, F.Gambineri, E.Bianchi, L.Rodriguez-Gallego, C.Zitnik, S.Vasconcelos, J.Guedes, M.Vitor, A.Marodi, L.Chapel, H.Reid, B.Roifman, C.Nadal, D.Reichenbach, J.Caragol, I.Garty, B.Dogu, F.Camcioglu, Y.Gülle, S.Sanal, O.Fischer, A.Abel, L.Stockinger, B.Picard, C.Casanova, J.2012-03-262012-03-262008-07J Exp Med. 2008 Jul 7;205(7):1543-500022-1007http://hdl.handle.net/10400.16/900Abstract 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.engjournal article