GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans
Authors
- Y. Yao
- P. Du Jiang
- B.N. Chao
- D. Cagdas
- S. Kubo
- A. Balasubramaniyam
- Y. Zhang
- B. Shadur
- A. NaserEddin
- L.R. Folio
- B. Schwarz
- E. Bohrnsen
- L. Zheng
- M. Lynberg
- S. Gottlieb
- M.A. Leney-Greene
- A.Y. Park
- I. Tezcan
- A. Akdogan
- R. Gocmen
- S. Onder
- A. Rosenberg
- E.J. Soilleux
- E. Johnson
- P.K. Jackson
- J. Demeter
- S.D. Chauvin
- F. Paul
- M. Selbach
- H. Bulut
- M.R. Clatworthy
- Z.K. Tuong
- H. Zhang
- B.J. Stewart
- C.M. Bosio
- P. Stepensky
- S. Clare
- S. Ganesan
- J.C. Pascall
- O. Daumke
- G.W. Butcher
- A.J. McMichael
- A.K. Simon
- M.J. Lenardo
Journal
- Journal of Experimental Medicine
Citation
- J Exp Med 219 (6): e20201405
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.