GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans-Reference-Cited by-同舟云学术

GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans

Published:2022-05-13 Issue:6 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Yao Yikun¹²^ORCID,Du Jiang Ping¹²^ORCID,Chao Brittany N.¹²³⁴^ORCID,Cagdas Deniz⁵⁶⁷^ORCID,Kubo Satoshi¹²^ORCID,Balasubramaniyam Arasu⁸⁹^ORCID,Zhang Yu¹⁰^ORCID,Shadur Bella¹¹¹²¹³^ORCID,NaserEddin Adeeb¹¹^ORCID,Folio Les R.¹⁴,Schwarz Benjamin¹⁵^ORCID,Bohrnsen Eric¹⁵^ORCID,Zheng Lixin¹²^ORCID,Lynberg Matthew¹²^ORCID,Gottlieb Simone¹²^ORCID,Leney-Greene Michael A.¹¹⁰^ORCID,Park Ann Y.¹²^ORCID,Tezcan Ilhan⁵⁶⁷^ORCID,Akdogan Ali¹⁶,Gocmen Rahsan¹⁷^ORCID,Onder Sevgen¹⁸^ORCID,Rosenberg Avi¹⁹²⁰,Soilleux Elizabeth J.²¹^ORCID,Johnson Errin²²^ORCID,Jackson Peter K.²³^ORCID,Demeter Janos²³^ORCID,Chauvin Samuel D.¹²^ORCID,Paul Florian⁸^ORCID,Selbach Matthias⁸²⁴^ORCID,Bulut Haydar⁸⁹^ORCID,Clatworthy Menna R.²⁵²⁶^ORCID,Tuong Zewen K.²⁵²⁶^ORCID,Zhang Hanlin⁴,Stewart Benjamin J.²⁵²⁶^ORCID,Bosio Catharine M.¹⁵^ORCID,Stepensky Polina¹¹^ORCID,Clare Simon²⁷^ORCID,Ganesan Sundar²⁸^ORCID,Pascall John C.²⁹^ORCID,Daumke Oliver⁸⁹^ORCID,Butcher Geoffrey W.²⁹^ORCID,McMichael Andrew J.³^ORCID,Simon Anna Katharina⁴^ORCID,Lenardo Michael J.¹²^ORCID

Affiliation:

1. Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1

2. National Institute of Allergy and Infectious Diseases Clinical Genomics Program, Rockville, MD 2

3. Nuffield Department of Medicine Research Building, Roosevelt Drive, Nuffield Department of Medicine, University of Oxford, Oxford, UK 3

4. Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, UK 4

5. Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey 5

6. Department of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey 6

7. Ihsan Dogramaci Childrens Hospital, Hacettepe University Faculty of Medicine, Ankara, Turkey 7

8. Crystallography, Max-Delbrück-Centrum for Molecular Medicine in the Helmholtz Association, Berlin, Germany 8

9. Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 6, Berlin, Germany 9

10. Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, MD 10

11. Hadassah University Medical Center, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Jerusalem, Israel 11

12. The Garvan Institute of Medical Research, Immunology Division, Darlinghurst, Sydney, Australia 12

13. St Vincent’s Clinical School, University of New South Wales, Darlinghurst, Sydney, Australia 13

14. Clinical Center, National Institutes of Health, Bethesda, MD 14

15. Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Rockville, MD 15

16. Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey 16

17. Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey 17

18. Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey 18

19. Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 19

20. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 20

21. Department of Pathology, University of Cambridge, Cambridge, UK 21

22. The Dunn School of Pathology, South Parks Road, Oxford, UK 22

23. Baxter Laboratory, Departments of Microbiology & Immunology and Pathology Stanford University School of Medicine, Stanford, CA 23

24. Charité Universitätsmedizin Berlin, Berlin, Germany 24

25. Molecular Immunity Unit, University of Cambridge Department of Medicine, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK 25

26. Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK 26

27. Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, UK 27

28. Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD 28

29. Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UK 29

Abstract

Inborn errors of immunity (IEIs) unveil regulatory pathways of human immunity. We describe a new IEI caused by mutations in the GTPase of the immune-associated protein 6 (GIMAP6) gene in patients with infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis. Patients and Gimap6−/− mice show defects in autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids. We find that GIMAP6 complexes with GABARAPL2 and GIMAP7 to regulate GTPase activity. Also, GIMAP6 is induced by IFN-γ and plays a critical role in antibacterial immunity. Finally, we observed that Gimap6−/− mice died prematurely from microangiopathic glomerulosclerosis most likely due to GIMAP6 deficiency in kidney endothelial cells.

Funder

Division of Intramural Research

National Institute of Allergy and Infectious Diseases

Oxford University

German Research Foundation

Hacettepe University Coordination Unit for Scientific Research Projects

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

https://rupress.org/jem/article-pdf/doi/10.1084/jem.20201405/1441332/jem_20201405.pdf