2. Academic Validation
  3. Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis

Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis

  • Sci Transl Med. 2020 Apr 8;12(538):eaay1620. doi: 10.1126/scitranslmed.aay1620.
Ping-Min Chen 1,  Parker C Wilson 2,  Justin A Shyer 1,  Margaret Veselits 3,  Holly R Steach 1,  Can Cui 1,  Gilbert Moeckel 2,  Marcus R Clark 3,  Joe Craft 4 5
Affiliations

Affiliations

  • 1 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 2 Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 3 Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, IL 60637, USA.
  • 4 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. [email protected].
  • 5 Department of Internal Medicine (Rheumatology, Allergy and Immunology), Yale University School of Medicine, New Haven, CT 06520, USA.
PMID: 32269165 DOI: 10.1126/scitranslmed.aay1620
Abstract

The kidney is a frequent target of autoimmune injury, including in systemic lupus erythematosus; however, how immune cells adapt to kidney's unique environment and contribute to tissue damage is unknown. We found that renal tissue, which normally has low oxygen tension, becomes more hypoxic in lupus nephritis. In the injured mouse tissue, renal-infiltrating CD4+ and CD8+ 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.

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