Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis-Reference-Cited by-全球学者库

Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis

Published:2022-11-03 Issue:1 Volume:220 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Ogishi Masato¹²^ORCID,Yang Rui¹^ORCID,Rodriguez Rémy³⁴^ORCID,Golec Dominic P.⁵^ORCID,Martin Emmanuel³⁴^ORCID,Philippot Quentin⁴⁶^ORCID,Bohlen Jonathan⁴⁶^ORCID,Pelham Simon J.¹^ORCID,Arias Andrés Augusto¹⁷⁸^ORCID,Khan Taushif⁹^ORCID,Ata Manar⁹^ORCID,Al Ali Fatima⁹^ORCID,Rozenberg Flore¹⁰^ORCID,Kong Xiao-Fei¹^ORCID,Chrabieh Maya⁴⁶^ORCID,Laine Candice⁴⁶^ORCID,Lei Wei-Te¹^ORCID,Han Ji Eun¹^ORCID,Seeleuthner Yoann⁴⁶^ORCID,Kaul Zenia⁵^ORCID,Jouanguy Emmanuelle¹⁴⁶^ORCID,Béziat Vivien⁴⁶^ORCID,Youssefian Leila¹¹¹²^ORCID,Vahidnezhad Hassan¹¹¹²^ORCID,Rao V. Koneti¹³^ORCID,Neven Bénédicte¹⁴^ORCID,Fieschi Claire¹⁵¹⁶^ORCID,Mansouri Davood¹⁷^ORCID,Shahrooei Mohammad¹⁸^ORCID,Pekcan Sevgi¹⁹^ORCID,Alkan Gulsum²⁰^ORCID,Emiroğlu Melike²⁰^ORCID,Tokgöz Hüseyin²¹^ORCID,Uitto Jouni¹¹¹²^ORCID,Hauck Fabian³⁴²²^ORCID,Bustamante Jacinta¹⁴⁶²³^ORCID,Abel Laurent¹⁴⁶^ORCID,Keles Sevgi²⁴^ORCID,Parvaneh Nima²⁵²⁶^ORCID,Marr Nico⁹²⁷^ORCID,Schwartzberg Pamela L.⁵^ORCID,Latour Sylvain³⁴^ORCID,Casanova Jean-Laurent¹⁴⁶²⁸²⁹^ORCID,Boisson-Dupuis Stéphanie¹⁴⁶^ORCID

Affiliation:

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

2. The David Rockefeller Graduate Program, Rockefeller University, New York, NY 2

3. Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR1163, Paris, France 3

4. Imagine Institute, University of Paris Cité, Paris, France 4

5. Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 5

6. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France 6

7. Primary Immunodeficiencies Group, University of Antioquia UdeA, Medellin, Colombia 7

8. School of Microbiology, University of Antioquia UdeA, Medellin, Colombia 8

9. Department of Immunology, Research Branch, Sidra Medicine, Doha, Qatar 9

10. Department of Virology, Cochin Hospital, University of Paris, Paris, France 10

11. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Philadelphia, PA 11

12. Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 12

13. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 13

14. Pediatric Immunology and Hematology Department, Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France 14

15. Clinical Immunology Department, Saint Louis Hospital, AP-HP Université de Paris, Paris, France 15

16. INSERM UMR1126, Institut de Recherche Saint-Louis, Université de Paris, Paris, France 16

17. Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 17

18. Department of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology, KU Leuven, Leuven, Belgium 18

19. Department of Pediatric Pulmonology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey 19

20. Division of Pediatric Infectious Diseases, Department of Pediatrics, Selcuk University Faculty of Medicine, Konya, Turkey 20

21. Department of Pediatric Hematology, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey 21

22. Division of Pediatric Immunology and Rheumatology, Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany 22

23. Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France 23

24. Division of Pediatric Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey 24

25. Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran 25

26. Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran 26

27. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar 27

28. Department of Pediatrics, Necker Hospital for Sick Children, Paris, France 28

29. Howard Hughes Medical Institute, New York, NY 29

Abstract

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4−CD8− double-negative (DN) αβ and Vδ2− γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES− phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients’ T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients’ total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αβ T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ–producing T cell subsets, thereby underlying TB.

Funder

St. Giles Foundation

Rockefeller University

Institut National de la Santé et de la Recherche Médicale

National Institute of Allergy and Infectious Diseases

National Center for Research Resources

National Center for Advancing Sciences of the National Institutes of Health

French National Research Agency

French Foundation for Medical Research

Funai Foundation for Information Technology

Honjo International Scholarship Foundation

National Cancer Institute