Details

Autor(en) / Beteiligte

• de Beaucoudrey, Ludovic
• Puel, Anne
• Filipe-Santos, Orchidée
• Cobat, Aurélie
• Ghandil, Pegah
• Chrabieh, Maya
• Feinberg, Jacqueline
• von Bernuth, Horst
• Samarina, Arina
• Jannière, Lucile
• Fieschi, Claire
• Stéphan, Jean-Louis
• Boileau, Catherine
• Lyonnet, Stanislas
• Jondeau, Guillaume
• Cormier-Daire, Valérie
• Le Merrer, Martine
• Hoarau, Cyrille
• Lebranchu, Yvon
• Lortholary, Olivier
• Chandesris, Marie-Olivia
• Tron, François
• Gambineri, Eleonora
• Bianchi, Lucia
• Rodriguez-Gallego, Carlos
• Zitnik, Simona E
• Vasconcelos, Julia
• Guedes, Margarida
• Vitor, Artur Bonito
• Marodi, Laszlo
• Chapel, Helen
• Reid, Brenda
• Roifman, Chaim
• Nadal, David
• Reichenbach, Janine
• Caragol, Isabel
• Garty, Ben-Zion
• Dogu, Figen
• Camcioglu, Yildiz
• Gülle, Sanyie
• Sanal, Ozden
• Fischer, Alain
• Abel, Laurent
• Stockinger, Birgitta
• Picard, Capucine
• Casanova, Jean-Laurent

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2008-07, Vol.205 (7), p.1543-1550

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.