GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans.
Yikun YaoPing Du JiangBrittany N ChaoDeniz Çağdaş AyvazYasuyuki TodorokiArasu BalasubramaniyamYu ZhangBella ShadurAdeeb Naser EddinLes R FolioBenjamin SchwarzEric BohrnsenMichael J LenardoMatthew LynbergSimone GottliebMichael A Leney-GreeneAnn Y ParkF İlhan TezcanAli AkdoganRahşan GocmenSevgen Celik OnderAvi RosenbergElizabeth J SoilleuxErrin JohnsonPeter K JacksonJanos DemeterSamuel D ChauvinFlorian PaulMatthias SelbachHaydar BulutMenna R ClatworthyZewen Kelvin TuongHanlin ZhangBenjamin J StewartCatharine M BosioPolina StepenskySimon ClareSundar GanesanJohn C PascallOliver DaumkeGeoffrey W ButcherAndrew J McMichaelAnna Katharina SimonMichael J LenardoPublished in: The Journal of experimental medicine (2022)
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.
Keyphrases
- fatty acid
- endothelial cells
- oxidative stress
- high fat diet induced
- cell death
- end stage renal disease
- endoplasmic reticulum stress
- ejection fraction
- signaling pathway
- newly diagnosed
- chronic kidney disease
- emergency department
- dendritic cells
- type diabetes
- immune response
- copy number
- adipose tissue
- patient reported outcomes
- insulin resistance
- patient safety
- peritoneal dialysis
- electronic health record