| Literature DB >> 35551368 |
Yikun Yao1,2, Ping Du Jiang1,2, Brittany N Chao1,2,3,4, Deniz Cagdas5,6,7, Andrew J McMichael3, Anna Katharina Simon4, Michael J Lenardo1,2, Satoshi Kubo1,2, Arasu Balasubramaniyam8,9, Yu Zhang10, Bella Shadur11,12,13, Adeeb NaserEddin11, Les R Folio14, Benjamin Schwarz15, Eric Bohrnsen15, Lixin Zheng1,2, Matthew Lynberg1,2, Simone Gottlieb1,2, Michael A Leney-Greene1,10, Ann Y Park1,2, Ilhan Tezcan5,6,7, Ali Akdogan16, Rahsan Gocmen17, Sevgen Onder18, Avi Rosenberg19,20, Elizabeth J Soilleux21, Errin Johnson22, Peter K Jackson23, Janos Demeter23, Samuel D Chauvin1,2, Florian Paul8, Matthias Selbach8,24, Haydar Bulut8,9, Menna R Clatworthy25,26, Zewen K Tuong25,26, Hanlin Zhang4, Benjamin J Stewart25,26, Catharine M Bosio15, Polina Stepensky11, Simon Clare27, Sundar Ganesan28, John C Pascall29, Oliver Daumke8,9, Geoffrey W Butcher29.
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. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.Entities:
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Year: 2022 PMID： 35551368 PMCID： PMC9111091 DOI： 10.1084/jem.20201405
Source DB: PubMed Journal: J Exp Med ISSN： 0022-1007 Impact factor: 17.579