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A Recessive Form of Hyper-Ige Syndrome by Disruption of Znf341-Dependent Stat3 Transcription and Activity Publisher Pubmed



Beziat V1, 2 ; Li J3 ; Lin JX4 ; Ma CS5, 6 ; Li P4 ; Bousfiha A7 ; Pellier I8 ; Zoghi S9, 10, 11 ; Baris S12 ; Keles S13 ; Gray P14, 15 ; Du N4 ; Wang Y1, 2 ; Zerbib Y1, 2 Show All Authors
Authors
  1. Beziat V1, 2
  2. Li J3
  3. Lin JX4
  4. Ma CS5, 6
  5. Li P4
  6. Bousfiha A7
  7. Pellier I8
  8. Zoghi S9, 10, 11
  9. Baris S12
  10. Keles S13
  11. Gray P14, 15
  12. Du N4
  13. Wang Y1, 2
  14. Zerbib Y1, 2
  15. Levy R1, 2
  16. Leclercq T1, 2
  17. About F1, 2
  18. Lim AI16, 17
  19. Rao G5
  20. Payne K5
  21. Pelham SJ5, 6
  22. Avery DT5
  23. Deenick EK5, 6
  24. Pillay B5, 6
  25. Chou J18, 19
  26. Guery R1, 2, 20
  27. Belkadi A1, 2
  28. Guerin A1, 2
  29. Migaud M1, 2
  30. Rattina V1, 2
  31. Ailal F7
  32. Benhsaien I7
  33. Bouaziz M1, 2
  34. Habib T21
  35. Chaussabel D21
  36. Marr N21
  37. Elbenna J22
  38. Grimbacher B23
  39. Wargon O24
  40. Bustamante J1, 2, 3, 25
  41. Boisson B1, 2, 3
  42. Mullerfleckenstein I26
  43. Fleckenstein B26
  44. Chandesris MO27, 28
  45. Titeux M2, 29
  46. Fraitag S30
  47. Alyanakian MA31
  48. Leruezville M32, 33
  49. Picard C2, 25, 33, 34
  50. Meyts I35
  51. Di Santo JP16, 17
  52. Hovnanian A2, 29, 36
  53. Somer A37
  54. Ozen A12
  55. Rezaei N9, 10, 11
  56. Chatila TA18, 19
  57. Abel L1, 2, 3
  58. Leonard WJ4
  59. Tangye SG5, 6
  60. Puel A1, 2, 3
  61. Casanova JL1, 2, 3, 34, 38
Show Affiliations
Authors Affiliations
  1. 1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, 75015, France
  2. 2. Paris Descartes University, Imagine Institute, Paris, 75015, France
  3. 3. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, 10065, NY, United States
  4. 4. Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20892–1674, MD, United States
  5. 5. Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, 2010, NSW, Australia
  6. 6. St. Vincent’s Clinical School, University of New South Wales, Sydney, 2052, NSW, Australia
  7. 7. Clinical Immunology Unit, Casablanca Children’s Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco
  8. 8. Pedi-atric Hemato-Oncology Unit, University Hospital of Angers, Angers, 49933, France
  9. 9. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
  10. 10. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, 1419733151, Iran
  11. 11. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Marmara University School of Medicine, Department of Pediatrics, Division of Allergy and Immunology, Istanbul, 34899, Turkey
  13. 13. Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, 42060, Turkey
  14. 14. Department of Immunology and Infectious Diseases, Sydney Children’s Hospital, Randwick, 2031, NSW, Australia
  15. 15. School of Women’s and Children’s Health, University of New South Wales School of Women’s and Children’s Health, Sydney, 2031, NSW, Australia
  16. 16. Innate Immunity Unit, Institut Pasteur, Paris, 75015, France
  17. 17. INSERM U1223, Paris, 75015, France
  18. 18. Division of Immunology, Boston Children’s Hospital, Boston, 02115, MA, United States
  19. 19. Department of Pediatrics, Harvard Medical School, Boston, 02115, MA, United States
  20. 20. Unit of Tropical and Infectious Diseases, Necker Hospital for Sick Children, Assistance Pub-lique–Hopitaux de Paris (AP-HP), Paris, 75015, France
  21. 21. Sidra Medicine, Doha, Qatar
  22. 22. INSERM-U1149, CNRS-ERL8252, Center for Research on Inflammation, Labex Inflamex, Paris Diderot University, Faculte de Medecine, Xavier Bichat Medical School, Paris, 75018, France
  23. 23. Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, 79106, Germany
  24. 24. Department of Paediatric Dermatology, Sydney Children’s Hospital, High Street, Randwick, 2031, NSW, Australia
  25. 25. Study Center for Immunodeficiency, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  26. 26. Institute of Clinical and Molecular Virology, University of Erlangen-Nurnberg, Erlangen, D-91054, Germany
  27. 27. Department of Hematology, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  28. 28. Referral Center for Immunodeficiency, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  29. 29. Laboratory of Genetic Skin Diseases: from Disease Mechanism to Therapies, INSERM U1163, Paris, 75015, France
  30. 30. Department of Pathology, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  31. 31. Immunology Laboratory, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  32. 32. Virology Laboratory, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  33. 33. Paris Descartes University, EA 73-28, Paris, 75015, France
  34. 34. Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  35. 35. Department of Immunology and Microbiology, Childhood Immunology, Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, 3000, Belgium
  36. 36. Department of Genetics, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  37. 37. Istanbul University, Istanbul Medical Faculty, Division of Infectious Diseases and Immunology, Istanbul, 34452, Turkey
  38. 38. Howard Hughes Medical Institute, New York, 10065, NY, United States

Source: Science Immunology Published:2018


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. Copyright © 2018 The Authors, some rights reserved.
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