| Literature DB >> 29907691 |
Vivien Béziat1,2, Juan Li3, Jian-Xin Lin4, Cindy S Ma5,6, Peng Li4, Aziz Bousfiha7, Isabelle Pellier8, Samaneh Zoghi9,10,11, Safa Baris12, Sevgi Keles13, Paul Gray14,15, Ning Du4, Yi Wang16,2, Yoann Zerbib16,2, Romain Lévy16,2, Thibaut Leclercq16,2, Frédégonde About16,2, Ai Ing Lim17,18, Geetha Rao5, Kathryn Payne5, Simon J Pelham5,6, Danielle T Avery5, Elissa K Deenick5,6, Bethany Pillay5,6, Janet Chou19,20, Romain Guery16,2,21, Aziz Belkadi16,2, Antoine Guérin16,2, Mélanie Migaud16,2, Vimel Rattina16,2, Fatima Ailal7, Ibtihal Benhsaien7, Matthieu Bouaziz16,2, Tanwir Habib22, Damien Chaussabel22, Nico Marr22, Jamel El-Benna23, Bodo Grimbacher24, Orli Wargon25, Jacinta Bustamante16,2,3,26, Bertrand Boisson16,2,3, Ingrid Müller-Fleckenstein27, Bernhard Fleckenstein27, Marie-Olivia Chandesris28,29, Matthias Titeux2,30, Sylvie Fraitag31, Marie-Alexandra Alyanakian32, Marianne Leruez-Ville33,34, Capucine Picard2,26,34,35, Isabelle Meyts36, James P Di Santo17,18, Alain Hovnanian2,30,37, Ayper Somer38, Ahmet Ozen12, Nima Rezaei9,10,11, Talal A Chatila19,20, Laurent Abel16,2,3, Warren J Leonard4, Stuart G Tangye5,6, Anne Puel1,2,3, Jean-Laurent Casanova1,2,3,35,39.
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 (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.Entities:
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Year: 2018 PMID： 29907691 PMCID： PMC6141026 DOI： 10.1126/sciimmunol.aat4956
Source DB: PubMed Journal: Sci Immunol ISSN： 2470-9468