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

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish
Article numbereaay1620
JournalScience translational medicine
Volume12
Issue number538
DOIs
StatePublished - Apr 8 2020

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    Chen, P. M., Wilson, P. C., Shyer, J. A., Veselits, M., Steach, H. R., Cui, C., Moeckel, G., Clark, M. R., & Craft, J. (2020). Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis. Science translational medicine, 12(538), [eaay1620]. https://doi.org/10.1126/scitranslmed.aay1620