Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis
Ping-Min Chen, Parker C. Wilson, Justin A. Shyer, Margaret Veselits, Holly R. Steach, Can Cui, Gilbert Moeckel, Marcus R. Clark, Joe Craft
Abstract
T cells express hypoxia-inducible factor-1 (HIF-1), which alters their cellular metabolism and prevents their apoptosis in hypoxia. HIF-1-dependent gene-regulated pathways were also up-regulated in renal-infiltrating T cells in human lupus nephritis. Perturbation of these environmental adaptations by selective HIF-1 blockade inhibited infiltrating T cells and reversed tissue hypoxia and injury in murine models of lupus. The results suggest that targeting HIF-1 might be effective for treating renal injury in autoimmune diseases.
Topics & Concepts
Lupus nephritisEffectorKidneySystemic lupus erythematosusHypoxia (environmental)BlockadeCell injuryImmunologyNephritisMedicinePathologyBiologyCell biologyChemistryReceptorInternal medicineApoptosisDiseaseBiochemistryOxygenOrganic chemistryCancer, Hypoxia, and MetabolismImmune cells in cancerLipid metabolism and disorders