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

• DOI: 10.1084/jem.20080321
• Publication Date: 2008-07-01T23:56:29Z
• Authors: Ludovic de Beauco...; Anne Puel; Orchidée Filipe-...; Aurélie Cobat; Pegah Ghandil; Maya Chrabieh; Jacqueline Feinberg; Horst von Bernuth; Arina Samarina; Lucile Jannière; Claire Fieschi; Jean-Louis Stéphan; Catherine Boileau; Stanislas Lyonnet; Guillaume Jondeau; Valérie Cormier-...; Martine Le Merrer; Cyrille Hoarau; Yvon Lebranchu; Olivier Lortholary; Marie-Olivia Chan...; François Tron; Eleonora Gambineri; Lucia Bianchi; Carlos Rodriguez-...; Simona E. Zitnik; Julia Vasconcelos; Margarida Guedes; Artur Bonito Vitor; Laszlo Marodi; Helen Chapel; Brenda Reid; Chaim Roifman; David Nadal; Janine Reichenbach; Isabel Caragol; Ben-Zion Garty; Figen Dogu; Yildiz Camcioglu; Sanyie Gülle; Ozden Sanal; Alain Fischer; Laurent Abel; Birgitta Stockinger; Capucine Picard; Jean-Laurent Casa...
• Keywords: Male; STAT3 Transcription Factor; Quantitative Trait Loci; T cells; Receptor, Transforming Growth Factor-beta Type I; 610 Medicine & health; Protein Serine-Threonine Kinases; STAT3; 03 medical and health sciences; Humans; 3205 Medicina interna; 2403 Immunology; 0303 health sciences; Interleukin-17; IL12RB1; Genetic Diseases, Inborn; Receptor, Transforming Growth Factor-beta Type II; Receptors, Interleukin-12; Cell Differentiation; T-Lymphocytes, Helper-Inducer; 3. Good health; Interleukin-1 Receptor-Associated Kinases; 10036 Medical Clinic; Mutation; Myeloid Differentiation Factor 88; 2723 Immunology and Allergy; Brief Definitive Reports; Cytokines; Female; 32 Ciencias médicas; Receptors, Transforming Growth Factor beta; Signal Transduction

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed question IL-17–producing vivo by quantifying production and secretion IL-17 fresh ex vivo, cell blasts expanded from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations TGFB1, TGFBR1, TGFBR2 (Camurati-Engelmann disease Marfan-like syndromes) loss-of-function IRAK4 MYD88 (Mendelian predisposition pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, a lesser extent, null IL12B IL12RB1 susceptibility mycobacterial diseases) impaired cells. These data suggest that IL-12Rβ1– STAT-3–dependent signals play key role differentiation and/or expansion populations vivo.