Journal
SCIENCE IMMUNOLOGY
Volume 3, Issue 24, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aat4956
Keywords
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Categories
Funding
- INSERM
- Paris Descartes University
- Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- Jeffrey Modell Foundation Translational Research Program
- French National Research Agency (ANR) [GENCMCD-ANR-11-BSV3-005-01, HGDIFD-ANR-14-CE15-0006-01, NKIR-ANR-13-PDOC-0025-01, EURO-CMC-ANR-14-RARE-0005-02]
- Investissement d'avenir program [ANR-10-IAHU-01]
- National Institute of Allergy and Infectious Diseases of the NIH [U01AI109697, R01AI127564, 5R01AI065617]
- Rockefeller University
- Howard Hughes Medical Institute
- St. Giles Foundation
- Institut Pasteur
- FP7 [305578, 317057]
- ANR [NKIR-ANR-13-PDOC-0025-01]
- INSERM Ph.D. program (Poste d'Accueil INSERM)
- Fulbright grant (Franco-American commission)
- Philippe Foundation
- French National Agency for Research on AIDS and Viral Hepatitis (ANRS) [13318]
- Fondation pour la Recherche Medicale (FRM) [FDM20140630671]
- IFNGPHOX grant from ANR [ANR13-ISV3-0001-01]
- BMBF (German Federal Ministry of Education and Research) [01E01303, 01ZX1306F]
- klinische onderzoeks-en opleidingsraad (clinical research council) grant from UZ Leuven
- klinisch onderzoeksfonds (clinical research fund) grant from KU Leuven
- International Mobility Grant from Fonds voor Wetenschappelijk Onderzoek (fund for scientific research) Vlaanderen
- National Health and Medical Research Council of Australia
- Office of Health and Medical Research of the NSW Government
- Jeffrey Modell Foundation
- John Cook Brown Foundation
- European Union's Seventh Framework Program [317057]
- Scientific and Technological Research Council of Turkey [1059B191300622]
- Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH
- AP-HP interface contract
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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(H)17) cells, have an excess of T(H)2 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.
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