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

• Autor(a) principal: Beaucoudrey, L.
• Data de Publicação: 2008
• Outros Autores: 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.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/900

Abstract 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.