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

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-/- mi...

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Bibliographic Details
Published in:The Journal of experimental medicine 2022-06, Vol.219 (6)
Main Authors: Yao, Yikun, Du Jiang, Ping, Chao, Brittany N, Cagdas, Deniz, Kubo, Satoshi, Balasubramaniyam, Arasu, Zhang, Yu, Shadur, Bella, NaserEddin, Adeeb, Folio, Les R, Schwarz, Benjamin, Bohrnsen, Eric, Zheng, Lixin, Lynberg, Matthew, Gottlieb, Simone, Leney-Greene, Michael A, Park, Ann Y, Tezcan, Ilhan, Akdogan, Ali, Gocmen, Rahsan, Onder, Sevgen, Rosenberg, Avi, Soilleux, Elizabeth J, Johnson, Errin, Jackson, Peter K, Demeter, Janos, Chauvin, Samuel D, Paul, Florian, Selbach, Matthias, Bulut, Haydar, Clatworthy, Menna R, Tuong, Zewen K, Zhang, Hanlin, Stewart, Benjamin J, Bosio, Catharine M, Stepensky, Polina, Clare, Simon, Ganesan, Sundar, Pascall, John C, Daumke, Oliver, Butcher, Geoffrey W, McMichael, Andrew J, Simon, Anna Katharina, Lenardo, Michael J
Format: Article
Language:English
Subjects:
Immunodeficiency
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20201405