Impaired IL-23–dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency-Reference-Cited by-同舟云学术

Impaired IL-23–dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency

Published:2022-09-12 Issue:10 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Ogishi Masato¹^ORCID,Arias Andrés Augusto¹²³^ORCID,Yang Rui¹^ORCID,Han Ji Eun¹^ORCID,Zhang Peng¹^ORCID,Rinchai Darawan¹^ORCID,Halpern Joshua¹^ORCID,Mulwa Jeanette¹^ORCID,Keating Narelle¹⁴^ORCID,Chrabieh Maya⁵⁶^ORCID,Lainé Candice⁵⁶^ORCID,Seeleuthner Yoann⁵⁶^ORCID,Ramírez-Alejo Noé¹^ORCID,Nekooie-Marnany Nioosha⁷^ORCID,Guennoun Andrea⁸^ORCID,Muller-Fleckenstein Ingrid⁹,Fleckenstein Bernhard⁹^ORCID,Kilic Sara S.¹⁰^ORCID,Minegishi Yoshiyuki¹¹^ORCID,Ehl Stephan¹²^ORCID,Kaiser-Labusch Petra¹³^ORCID,Kendir-Demirkol Yasemin¹⁴^ORCID,Rozenberg Flore¹⁵^ORCID,Errami Abderrahmane¹⁶^ORCID,Zhang Shen-Ying¹⁵⁶^ORCID,Zhang Qian¹⁵⁶^ORCID,Bohlen Jonathan⁵⁶^ORCID,Philippot Quentin⁵⁶^ORCID,Puel Anne¹⁵⁶^ORCID,Jouanguy Emmanuelle¹⁵⁶^ORCID,Pourmoghaddas Zahra¹⁷^ORCID,Bakhtiar Shahrzad¹⁸^ORCID,Willasch Andre M.¹⁸^ORCID,Horneff Gerd¹⁹²⁰^ORCID,Llanora Genevieve²¹^ORCID,Shek Lynette P.²¹²²^ORCID,Chai Louis Y.A.²³²⁴²⁵^ORCID,Tay Sen Hee²⁵²⁶^ORCID,Rahimi Hamid H.²⁷^ORCID,Mahdaviani Seyed Alireza²⁸^ORCID,Nepesov Serdar²⁹^ORCID,Bousfiha Aziz A.³⁰^ORCID,Erdeniz Emine Hafize³¹^ORCID,Karbuz Adem³²^ORCID,Marr Nico⁸^ORCID,Navarrete Carmen³³^ORCID,Adeli Mehdi³⁴^ORCID,Hammarstrom Lennart³⁵³⁶³⁷^ORCID,Abolhassani Hassan³⁵³⁷^ORCID,Parvaneh Nima³⁷^ORCID,Al Muhsen Saleh³⁸^ORCID,Alosaimi Mohammed F.³⁸^ORCID,Alsohime Fahad³⁹⁴⁰^ORCID,Nourizadeh Maryam⁴¹⁴²,Moin Mostafa⁴¹⁴²,Arnaout Rand⁴³⁴⁴^ORCID,Alshareef Saad⁴³^ORCID,El-Baghdadi Jamila⁴⁵^ORCID,Genel Ferah⁴⁶^ORCID,Sherkat Roya⁷^ORCID,Kiykim Ayça⁴⁷^ORCID,Yücel Esra⁴⁸^ORCID,Keles Sevgi⁴⁹^ORCID,Bustamante Jacinta¹⁵⁵⁰^ORCID,Abel Laurent¹⁵⁶^ORCID,Casanova Jean-Laurent¹⁵⁶⁵¹⁵²^ORCID,Boisson-Dupuis Stéphanie¹⁵⁶^ORCID

Affiliation:

1. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 1

2. Primary Immunodeficiencies Group, University of Antioquia, Medellin, Colombia 2

3. School of Microbiology, University of Antioquia, Medellin, Colombia 3

4. Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, Australia 4

5. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France 5

6. Paris Cité University, Imagine Institute, Paris, France 6

7. Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 7

8. Sidra Medicine, Doha, Qatar 8

9. Institute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany 9

10. Department of Pediatric Immunology and Rheumatology, Faculty of Medicine, Uludag University, Bursa, Turkey 10

11. Division of Molecular Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan 11

12. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany 12

13. Eltern- Kind -Zentrum Prof. Hess, Klinikum Bremen–Mitte, Bremen, Germany 13

14. Department of Pediatric Genetics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey 14

15. Laboratory of Virology, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France 15

16. Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco 16

17. Department of Pediatric Infectious Disease, Isfahan University of Medical Sciences, Isfahan, Iran 17

18. Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Department for Child and Adolescent Medicine, University Hospital Frankfurt, Frankfurt, Germany 18

19. Center for Pediatric Rheumatology, Department of Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany 19

20. Medical Faculty, University of Cologne, Cologne, Germany 20

21. Division of Allergy and Immunology, Department of Paediatrics, Khoo Teck Puat - National University Children’s Medical Institute, National University Health System, Singapore 21

22. Department of Pediatrics, National University of Singapore, Singapore 22

23. Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore 23

24. Synthetic Biology for Clinical and Technological Innovation, Life Sciences Institute; Synthetic Biology Translational Research Program, National University of Singapore 24

25. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore 25 , Singapore

26. Division of Rheumatology, Department of Medicine, National University Hospital, Singapore 26

27. Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran 27

28. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 28

29. Department of Pediatric Allergy and Immunology, Istanbul Medipol University, Istanbul, Turkey 29

30. Clinical Immunology Unit, Department of Pediatrics, King Hassan II University, Ibn-Rochd Hospital, Casablanca, Morocco 30

31. Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey 31

32. Division of Pediatric Infectious Diseases, Okmeydani Training and Research Hospital, University of Health Sciences, Istanbul, Turkey 32

33. Department of Immunology, Hospital de Niños Roberto del Río, Santiago de Chile, Chile 33

34. Division of Allergy and Immunology, Sidra Medicine/Hamad Medical Corp., Doha, Qatar 34

35. Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden 35

36. Beijing Genomics Institute, Shenzhen, China 36

37. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran 37

38. Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia 38

39. Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia 39

40. Pediatric Intensive Care Unit, King Saud University Medical City, Riyadh, Saudi Arabia 40

41. Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 41

42. 42Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

43. Section of Allergy & Immunology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia 43

44. Al Faisal University, Riyadh, Saudi Arabia 44

45. Genetics Unit, Mohamed V Military Hospital, Hay Riad, Rabat, Morocco 45

46. University of Health Sciences, Dr Behçet Uz Children’s Hospital, Division of Pediatric Immunology, Izmir, Turkey 46

47. Pediatric Allergy and Immunology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey 47

48. Division of Pediatric Allergy and Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey 48

49. Division of Pediatric Allergy and Immunology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey 49

50. Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France 50

51. Howard Hughes Medical Institute, New York, NY 51

52. 52Deparment of Pediatrics, Necker Hospital for Sick Children, Paris, France

Abstract

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

Funder

St. Giles Foundation

Rockefeller University

Howard Hughes Medical Institute

Institut National de la Santé et de la Recherche Médicale

University of Paris

Sidra Medicine

National Institute of Allergy and Infectious Diseases

National Center for Advancing Sciences

National Institutes of Health

Fisher Center for Alzheimer’s Research Foundation

Meyer Foundation