A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Vivien Béziat; Juan Li; Jian Xin Lin; Cindy S. Ma; Peng Li; Aziz Bousfiha; Isabelle Pellier; Samaneh Zoghi; Safa Baris; Sevgi Keles; Paul Gray; Ning Du; Yi Wang; Yoann Zerbib; Romain Lévy; Thibaut Leclercq; Frédégonde About; Ai Ing Lim; Geetha Rao; Kathryn Payne; Simon J. Pelham; Danielle T. Avery; Elissa K. Deenick; Bethany Pillay; Janet Chou; Romain Guery; Aziz Belkadi; Antoine Guérin; Mélanie Migaud; Vimel Rattina; Fatima Ailal; Ibtihal Benhsaien; Matthieu Bouaziz; Tanwir Habib; Damien Chaussabel; Nico Marr; Jamel El-Benna; Bodo Grimbacher; Orli Wargon; Jacinta Bustamante; Bertrand Boisson; Ingrid Müller-Fleckenstein; Bernhard Fleckenstein; Marie Olivia Chandesris; Matthias Titeux; Sylvie Fraitag; Marie Alexandra Alyanakian; Marianne Leruez-Ville; Capucine Picard; Isabelle Meyts; James P. Di Santo; Alain Hovnanian; Ayper Somer; Ahmet Ozen; Nima Rezaei; Talal A. Chatila; Laurent Abel; Warren J. Leonard; Stuart G. Tangye; Anne Puel; Jean Laurent Casanova

doi:10.1126/sciimmunol.aat4956

A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Vivien Béziat, Juan Li, Jian Xin Lin, Cindy S. Ma, Peng Li, Aziz Bousfiha, Isabelle Pellier, Samaneh Zoghi, Safa Baris, Sevgi Keles, Paul Gray, Ning Du, Yi Wang, Yoann Zerbib, Romain Lévy, Thibaut Leclercq, Frédégonde About, Ai Ing Lim, Geetha Rao, Kathryn PayneSimon J. Pelham, Danielle T. Avery, Elissa K. Deenick, Bethany Pillay, Janet Chou, Romain Guery, Aziz Belkadi, Antoine Guérin, Mélanie Migaud, Vimel Rattina, Fatima Ailal, Ibtihal Benhsaien, Matthieu Bouaziz, Tanwir Habib, Damien Chaussabel, Nico Marr, Jamel El-Benna, Bodo Grimbacher, Orli Wargon, Jacinta Bustamante, Bertrand Boisson, Ingrid Müller-Fleckenstein, Bernhard Fleckenstein, Marie Olivia Chandesris, Matthias Titeux, Sylvie Fraitag, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Capucine Picard, Isabelle Meyts, James P. Di Santo, Alain Hovnanian, Ayper Somer, Ahmet Ozen, Nima Rezaei, Talal A. Chatila, Laurent Abel, Warren J. Leonard, Stuart G. Tangye, Anne Puel, Jean Laurent Casanova

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Abstract

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper–immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients’ cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (T_H17) cells, have an excess of T_H2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription–dependent autoinduction and sustained activity of STAT3.

Original language	English (US)
Article number	eaat4956
Journal	Science immunology
Volume	3
Issue number	24
DOIs	https://doi.org/10.1126/sciimmunol.aat4956
State	Published - 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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10.1126/sciimmunol.aat4956

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Béziat, V., Li, J., Lin, J. X., Ma, C. S., Li, P., Bousfiha, A., Pellier, I., Zoghi, S., Baris, S., Keles, S., Gray, P., Du, N., Wang, Y., Zerbib, Y., Lévy, R., Leclercq, T., About, F., Lim, A. I., Rao, G., ... Casanova, J. L. (2018). A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Science immunology, 3(24), Article eaat4956. https://doi.org/10.1126/sciimmunol.aat4956

@article{c4b33ae7b11c4ddbb6b8c53ae04d8333,

title = "A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity",

abstract = "Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper–immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients{\textquoteright} cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription–dependent autoinduction and sustained activity of STAT3.",

author = "Vivien B{\'e}ziat and Juan Li and Lin, {Jian Xin} and Ma, {Cindy S.} and Peng Li and Aziz Bousfiha and Isabelle Pellier and Samaneh Zoghi and Safa Baris and Sevgi Keles and Paul Gray and Ning Du and Yi Wang and Yoann Zerbib and Romain L{\'e}vy and Thibaut Leclercq and Fr{\'e}d{\'e}gonde About and Lim, {Ai Ing} and Geetha Rao and Kathryn Payne and Pelham, {Simon J.} and Avery, {Danielle T.} and Deenick, {Elissa K.} and Bethany Pillay and Janet Chou and Romain Guery and Aziz Belkadi and Antoine Gu{\'e}rin and M{\'e}lanie Migaud and Vimel Rattina and Fatima Ailal and Ibtihal Benhsaien and Matthieu Bouaziz and Tanwir Habib and Damien Chaussabel and Nico Marr and Jamel El-Benna and Bodo Grimbacher and Orli Wargon and Jacinta Bustamante and Bertrand Boisson and Ingrid M{\"u}ller-Fleckenstein and Bernhard Fleckenstein and Chandesris, {Marie Olivia} and Matthias Titeux and Sylvie Fraitag and Alyanakian, {Marie Alexandra} and Marianne Leruez-Ville and Capucine Picard and Isabelle Meyts and {Di Santo}, {James P.} and Alain Hovnanian and Ayper Somer and Ahmet Ozen and Nima Rezaei and Chatila, {Talal A.} and Laurent Abel and Leonard, {Warren J.} and Tangye, {Stuart G.} and Anne Puel and Casanova, {Jean Laurent}",

note = "Publisher Copyright: Copyright {\textcopyright} 2018 The Authors, some rights reserved.",

year = "2018",

doi = "10.1126/sciimmunol.aat4956",

language = "English (US)",

volume = "3",

journal = "Science immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "24",

}

Béziat, V, Li, J, Lin, JX, Ma, CS, Li, P, Bousfiha, A, Pellier, I, Zoghi, S, Baris, S, Keles, S, Gray, P, Du, N, Wang, Y, Zerbib, Y, Lévy, R, Leclercq, T, About, F, Lim, AI, Rao, G, Payne, K, Pelham, SJ, Avery, DT, Deenick, EK, Pillay, B, Chou, J, Guery, R, Belkadi, A, Guérin, A, Migaud, M, Rattina, V, Ailal, F, Benhsaien, I, Bouaziz, M, Habib, T, Chaussabel, D, Marr, N, El-Benna, J, Grimbacher, B, Wargon, O, Bustamante, J, Boisson, B, Müller-Fleckenstein, I, Fleckenstein, B, Chandesris, MO, Titeux, M, Fraitag, S, Alyanakian, MA, Leruez-Ville, M, Picard, C, Meyts, I, Di Santo, JP, Hovnanian, A, Somer, A, Ozen, A, Rezaei, N, Chatila, TA, Abel, L, Leonard, WJ, Tangye, SG, Puel, A & Casanova, JL 2018, 'A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity', Science immunology, vol. 3, no. 24, eaat4956. https://doi.org/10.1126/sciimmunol.aat4956

TY - JOUR

T1 - A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

AU - Béziat, Vivien

AU - Li, Juan

AU - Lin, Jian Xin

AU - Ma, Cindy S.

AU - Li, Peng

AU - Bousfiha, Aziz

AU - Pellier, Isabelle

AU - Zoghi, Samaneh

AU - Baris, Safa

AU - Keles, Sevgi

AU - Gray, Paul

AU - Du, Ning

AU - Wang, Yi

AU - Zerbib, Yoann

AU - Lévy, Romain

AU - Leclercq, Thibaut

AU - About, Frédégonde

AU - Lim, Ai Ing

AU - Rao, Geetha

AU - Payne, Kathryn

AU - Pelham, Simon J.

AU - Avery, Danielle T.

AU - Deenick, Elissa K.

AU - Pillay, Bethany

AU - Chou, Janet

AU - Guery, Romain

AU - Belkadi, Aziz

AU - Guérin, Antoine

AU - Migaud, Mélanie

AU - Rattina, Vimel

AU - Ailal, Fatima

AU - Benhsaien, Ibtihal

AU - Bouaziz, Matthieu

AU - Habib, Tanwir

AU - Chaussabel, Damien

AU - Marr, Nico

AU - El-Benna, Jamel

AU - Grimbacher, Bodo

AU - Wargon, Orli

AU - Bustamante, Jacinta

AU - Boisson, Bertrand

AU - Müller-Fleckenstein, Ingrid

AU - Fleckenstein, Bernhard

AU - Chandesris, Marie Olivia

AU - Titeux, Matthias

AU - Fraitag, Sylvie

AU - Alyanakian, Marie Alexandra

AU - Leruez-Ville, Marianne

AU - Picard, Capucine

AU - Meyts, Isabelle

AU - Di Santo, James P.

AU - Hovnanian, Alain

AU - Somer, Ayper

AU - Ozen, Ahmet

AU - Rezaei, Nima

AU - Chatila, Talal A.

AU - Abel, Laurent

AU - Leonard, Warren J.

AU - Tangye, Stuart G.

AU - Puel, Anne

AU - Casanova, Jean Laurent

PY - 2018

Y1 - 2018

N2 - Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper–immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients’ cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription–dependent autoinduction and sustained activity of STAT3.

AB - Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper–immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients’ cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription–dependent autoinduction and sustained activity of STAT3.

UR - http://www.scopus.com/inward/record.url?scp=85052886349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052886349&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.aat4956

DO - 10.1126/sciimmunol.aat4956

M3 - Article

C2 - 29907691

AN - SCOPUS:85052886349

SN - 2470-9468

VL - 3

JO - Science immunology

JF - Science immunology

IS - 24

M1 - eaat4956

ER -

A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

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