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

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

The Journal of experimental medicine (2022-05-14)
Yikun Yao, Ping Du Jiang, Brittany N Chao, Deniz Cagdas, Satoshi Kubo, Arasu Balasubramaniyam, Yu Zhang, Bella Shadur, Adeeb NaserEddin, Les R Folio, Benjamin Schwarz, Eric Bohrnsen, Lixin Zheng, Matthew Lynberg, Simone Gottlieb, Michael A Leney-Greene, Ann Y Park, Ilhan Tezcan, Ali Akdogan, Rahsan Gocmen, Sevgen Onder, Avi Rosenberg, Elizabeth J Soilleux, Errin Johnson, Peter K Jackson, Janos Demeter, Samuel D Chauvin, Florian Paul, Matthias Selbach, Haydar Bulut, Menna R Clatworthy, Zewen K Tuong, Hanlin Zhang, Benjamin J Stewart, Catharine M Bosio, Polina Stepensky, Simon Clare, Sundar Ganesan, John C Pascall, Oliver Daumke, Geoffrey W Butcher, Andrew J McMichael, Anna Katharina Simon, Michael J Lenardo
PMID35551368
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.