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

Ludovic De Beaucoudtey, Anne Puel, Orchidée Filipe-Santos, Aurélie Cobat, Pegah Ghandil, Maya Chrabieh, Jacqueline Felnberg, Horst Von Bernuth, Arina Samarina, Lucile Jannière, Claire Fieschi, Jean Louis Stéphan, Catherine Boileau, Stanislas Lyonnet, Guillaume Jondeau, Valérie Cormier-Daire, Martine Le Merrer, Cyrille Hoarau, Yvon Lebranchu, Olivier LortholaryMarie Olivia Chandesris, François Tron, Eleonora Gambineri, Lucia Bianchi, Carlos Rodriguez-Gallego, Simona E. Zitnik, Julia Vasconcelos, Margarida Guedes, Artur Bonito Vitor, L. Máródi, 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 Casanova

Research output: Contribution to journalArticle

331 Citations (Scopus)

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) 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.

Original languageEnglish
Pages (from-to)1543-1550
Number of pages8
JournalJournal of Experimental Medicine
Volume205
Issue number7
DOIs
Publication statusPublished - Jul 7 2008

Fingerprint

Interleukin-17
Human Development
T-Lymphocytes
Mutation
Helper-Inducer T-Lymphocytes
Camurati-Engelmann Syndrome
Interleukin-23
Marfan Syndrome
Interleukins
Transforming Growth Factors
Interleukin-1
Bacterial Infections
Interleukin-6
Cytokines
Population

ASJC Scopus subject areas

  • Immunology

Cite this

De Beaucoudtey, L., Puel, A., Filipe-Santos, O., Cobat, A., Ghandil, P., Chrabieh, M., ... Casanova, J. L. (2008). Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. Journal of Experimental Medicine, 205(7), 1543-1550. https://doi.org/10.1084/jem.20080321

Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. / De Beaucoudtey, Ludovic; Puel, Anne; Filipe-Santos, Orchidée; Cobat, Aurélie; Ghandil, Pegah; Chrabieh, Maya; Felnberg, 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; Máródi, L.; 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.

In: Journal of Experimental Medicine, Vol. 205, No. 7, 07.07.2008, p. 1543-1550.

Research output: Contribution to journalArticle

De Beaucoudtey, L, Puel, A, Filipe-Santos, O, Cobat, A, Ghandil, P, Chrabieh, M, Felnberg, J, Von Bernuth, H, Samarina, A, Jannière, L, Fieschi, C, Stéphan, JL, Boileau, C, Lyonnet, S, Jondeau, G, Cormier-Daire, V, Le Merrer, M, Hoarau, C, Lebranchu, Y, Lortholary, O, Chandesris, MO, Tron, F, Gambineri, E, Bianchi, L, Rodriguez-Gallego, C, Zitnik, SE, Vasconcelos, J, Guedes, M, Vitor, AB, Máródi, L, Chapel, H, Reid, B, Roifman, C, Nadal, D, Reichenbach, J, Caragol, I, Garty, BZ, Dogu, F, Camcioglu, Y, Gülle, S, Sanal, O, Fischer, A, Abel, L, Stockinger, B, Picard, C & Casanova, JL 2008, 'Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells', Journal of Experimental Medicine, vol. 205, no. 7, pp. 1543-1550. https://doi.org/10.1084/jem.20080321
De Beaucoudtey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. Journal of Experimental Medicine. 2008 Jul 7;205(7):1543-1550. https://doi.org/10.1084/jem.20080321
De Beaucoudtey, Ludovic ; Puel, Anne ; Filipe-Santos, Orchidée ; Cobat, Aurélie ; Ghandil, Pegah ; Chrabieh, Maya ; Felnberg, 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 ; Máródi, L. ; 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. / Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. In: Journal of Experimental Medicine. 2008 ; Vol. 205, No. 7. pp. 1543-1550.
@article{0a7ada02d24c4bc888e4c98955f6a777,
title = "Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells",
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) 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.",
author = "{De Beaucoudtey}, Ludovic and Anne Puel and Orchid{\'e}e Filipe-Santos and Aur{\'e}lie Cobat and Pegah Ghandil and Maya Chrabieh and Jacqueline Felnberg and {Von Bernuth}, Horst and Arina Samarina and Lucile Janni{\`e}re and Claire Fieschi and St{\'e}phan, {Jean Louis} and Catherine Boileau and Stanislas Lyonnet and Guillaume Jondeau and Val{\'e}rie Cormier-Daire and {Le Merrer}, Martine and Cyrille Hoarau and Yvon Lebranchu and Olivier Lortholary and Chandesris, {Marie Olivia} and Fran{\cc}ois Tron and Eleonora Gambineri and Lucia Bianchi and Carlos Rodriguez-Gallego and Zitnik, {Simona E.} and Julia Vasconcelos and Margarida Guedes and Vitor, {Artur Bonito} and L. M{\'a}r{\'o}di and Helen Chapel and Brenda Reid and Chaim Roifman and David Nadal and Janine Reichenbach and Isabel Caragol and Garty, {Ben Zion} and Figen Dogu and Yildiz Camcioglu and Sanyie G{\"u}lle and Ozden Sanal and Alain Fischer and Laurent Abel and Birgitta Stockinger and Capucine Picard and Casanova, {Jean Laurent}",
year = "2008",
month = "7",
day = "7",
doi = "10.1084/jem.20080321",
language = "English",
volume = "205",
pages = "1543--1550",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells

AU - De Beaucoudtey, Ludovic

AU - Puel, Anne

AU - Filipe-Santos, Orchidée

AU - Cobat, Aurélie

AU - Ghandil, Pegah

AU - Chrabieh, Maya

AU - Felnberg, Jacqueline

AU - Von Bernuth, Horst

AU - Samarina, Arina

AU - Jannière, Lucile

AU - Fieschi, Claire

AU - Stéphan, Jean Louis

AU - Boileau, Catherine

AU - Lyonnet, Stanislas

AU - Jondeau, Guillaume

AU - Cormier-Daire, Valérie

AU - Le Merrer, Martine

AU - Hoarau, Cyrille

AU - Lebranchu, Yvon

AU - Lortholary, Olivier

AU - Chandesris, Marie Olivia

AU - Tron, François

AU - Gambineri, Eleonora

AU - Bianchi, Lucia

AU - Rodriguez-Gallego, Carlos

AU - Zitnik, Simona E.

AU - Vasconcelos, Julia

AU - Guedes, Margarida

AU - Vitor, Artur Bonito

AU - Máródi, L.

AU - Chapel, Helen

AU - Reid, Brenda

AU - Roifman, Chaim

AU - Nadal, David

AU - Reichenbach, Janine

AU - Caragol, Isabel

AU - Garty, Ben Zion

AU - Dogu, Figen

AU - Camcioglu, Yildiz

AU - Gülle, Sanyie

AU - Sanal, Ozden

AU - Fischer, Alain

AU - Abel, Laurent

AU - Stockinger, Birgitta

AU - Picard, Capucine

AU - Casanova, Jean Laurent

PY - 2008/7/7

Y1 - 2008/7/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=46949086109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46949086109&partnerID=8YFLogxK

U2 - 10.1084/jem.20080321

DO - 10.1084/jem.20080321

M3 - Article

C2 - 18591412

AN - SCOPUS:46949086109

VL - 205

SP - 1543

EP - 1550

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

ER -