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

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de Beaucoudrey L., Puel A., Filipe-Santos O., Cobat A., Ghandil P., Chrabieh M., ...Daha Fazla

JOURNAL OF EXPERIMENTAL MEDICINE, cilt.205, sa.7, ss.1543-1550, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 205 Sayı: 7
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1084/jem.20080321
  • Dergi Adı: JOURNAL OF EXPERIMENTAL MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1543-1550
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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-12R beta 1- 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.