Mutations In Stat3 And Il12Rb1 Impair The Development Of Human Il-17–Producing T Cells
Date
2008Author
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
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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) 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.
URI
https://doi.org/10.1084/jem.20080321https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442631/
http://hdl.handle.net/11655/14192