TY - JOUR
T1 - GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans
AU - Yao, Yikun
AU - Jiang, Pingdu
AU - Chao, Brittany N.
AU - Cagdas, Deniz
AU - Kubo, Satoshi
AU - Balasubramaniyam, Arasu
AU - Zhang, Yu
AU - Shadur, Bella
AU - Nasereddin, Adeeb
AU - Folio, Les R.
AU - Schwarz, Benjamin
AU - Bohrnsen, Eric
AU - Zheng, Lixin
AU - Lynberg, Matthew
AU - Gottlieb, Simone
AU - Leney-Greene, Michael A.
AU - Park, Ann Y.
AU - Tezcan, Ilhan
AU - Akdogan, Ali
AU - Gocmen, Rahsan
AU - Onder, Sevgen
AU - Rosenberg, Avi
AU - Soilleux, Elizabeth J.
AU - Johnson, Errin
AU - Jackson, Peter K.
AU - Demeter, Janos
AU - Chauvin, Samuel D.
AU - Paul, Florian
AU - Selbach, Matthias
AU - Bulut, Haydar
AU - Clatworthy, Menna R.
AU - Tuong, Zewen K.
AU - Zhang, Hanlin
AU - Stewart, Benjamin J.
AU - Bosio, Catharine M.
AU - Stepensky, Polina
AU - Clare, Simon
AU - Ganesan, Sundar
AU - Pascall, Johnc
AU - Daumke, Oliver
AU - Butcher, Geoffreyw
AU - McMichael, Andrew J.
AU - Simon, Anna Katharina
AU - Lenardo, Michael J.
N1 - Funding Information:
We thank the participating clinicians, nurses, laboratory staff, and the patients and their families. We thank Dr. Helen Su, Nancie Ann Mooney, and the Kennedy Institute of Rheumatology. Dr. Bella Shadur was supported by the Australian Government Research Training Program Scholarship and Hadassah. We thank Hyun-Hee Lee, Emilio Flano, and Merck, Inc. for support and Ryan Kissinger for help with illustrations.We thank the Infection and Immunity Immunophenotyping (3I) consortium led by Adrian Hayday (King’s College) for the KOMP Gimap6 mouse and associated data.
Funding Information:
This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, the Oxford University McMichael Research Fund, and the German Research Foundation (Collaborative Research Grant 958, Project A12). Projects 013 D08103 001-341, 11/19-23, and 16/9087 were generously funded by Hacettepe University Coordination Unit for Scientific Research Projects.
Publisher Copyright:
© 2022, Rockefeller University Press. All rights reserved.
PY - 2022/6/6
Y1 - 2022/6/6
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20201405
DO - 10.1084/jem.20201405
M3 - Article
C2 - 35551368
AN - SCOPUS:85132122477
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
M1 - e20201405
ER -