Autor(es):
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.
Data: 2008
Identificador Persistente: http://hdl.handle.net/10400.16/900
Origem: Repositório Científico da Unidade Local de Saúde de Santo António (ULSSA)
Descrição
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.
