Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Gating strategy for renal-infiltrating CD4+ and CD8+ T cells.
  • Fig. S2. Renal-infiltrating CD4+ and CD8+ T cells are functionally active and phenotypically distinct.
  • Fig. S3. Reversal of tissue damage and hypoxia after T cell depletion in lupus nephritis.
  • Fig. S4. Validation of hypoxic signatures in renal-infiltrating CD4+ and CD8+ T cells using a published transcriptome dataset.
  • Fig. S5. Illustration used to define renal pimonidazole staining.
  • Fig. S6. Regions of hypoxia extend to the renal cortex in murine lupus nephritis.
  • Fig. S7. Effect of hypoxia on T cell populations in lupus nephritis.
  • Fig. S8. Predominant HIF-1α but not HIF-2α expression in renal-infiltrating T cells.
  • Fig. S9. T cell depletion reverses renal cortical hypoxia.
  • Fig. S10. HIF-1–regulated survival pathway in renal-infiltrating T cells from B6.Sle1.Yaa lupus-prone mice.
  • Fig. S11. HIF-1–controlled survival pathways are up-regulated in hypoxia and pseudohypoxia T cell cultures.
  • Fig. S12. Alternative splicing of BNIP3 regulated by PDK2 promotes T cell survival in hypoxia.
  • Fig. S13. HIF-1–dependent T cell survival in renal hypoxia mediated by PDK2-driven alternative splicing of BNIP3.
  • Fig. S14. IDH1 and PRODH are up-regulated in renal-infiltrating T cells.
  • Fig. S15. PRODH is up-regulated in hypoxia and pseudohypoxia T cell cultures.
  • Fig. S16. Changes in mitochondrial function and glycolysis upon blocking proline metabolism in pseudohypoxia.
  • Fig. S17. HIF-1–controlled proline metabolism facilitates glycolysis.
  • Fig. S18. Validation of phenotypic analyses of renal-infiltrating CD4+ and CD8+ T cells using a published transcriptome dataset.
  • Fig. S19. Cellular adaptation in hypoxia is perturbed after selective HIF-1 blockade.
  • Fig. S20. Selective HIF-1 blockade is therapeutic in murine lupus nephritis.
  • Fig. S21. Phenotypic analyses of the nephritic lupus-prone mice treated with a HIF-1 antagonist.
  • Fig. S22. HIF-1 pharmacological blockade reduces autoantibody production and abolishes GC formation in murine lupus.
  • Fig. S23. Genetic ablation of HIF-1α in T cells reduces glycolytic capacity and tubulointerstitial infiltrations in lupus nephritis.
  • Fig. S24. Hypoxia-regulated T cell survival and effector transcripts in human lupus nephritis.
  • Fig. S25. Hypoxia-regulated proteins in noninflamed regions of human lupus nephritis.
  • Table S1. Up-regulated pathways in renal-infiltrating T cells in murine lupus nephritis.
  • Table S2. Targeted sequences for shRNA design.
  • Table S3. Primers for qPCR.
  • Legend for data file S1
  • References (6265)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1. Summary of the transcriptome data of kidney versus spleen T cells with respective fold changes and statistics (provided as separate Excel file).