Science Immunology

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Generation of humanized DITRA-like mice.
  • Fig. S2. Expression of members of IL-36 family in DITRA-like and WT mice at steady state and in the setting of IMQ-induced skin inflammation.
  • Fig. S3. IL-36R KO mice are protected from developing IMQ-induced skin inflammation in vivo.
  • Fig. S4. Skin homogenates derived from IMQ-treated DITRA-like mice potently stimulate HEK298 cells engineered to express hIL-36R in a dose-dependent and IL-36R–specific manner.
  • Fig. S5. Anti–hIL-36R antibody treatment ameliorates acute IMQ-induced skin inflammation in DITRA-like mice in a dose-dependent manner.
  • Fig. S6. Comparable efficacy of hIL-36R and mouse IL-12p40 blockade in acute IMQ-induced skin inflammation in DITRA-like mice.
  • Fig. S7. Comparable inhibition of IMQ transcriptional signature with hIL-36R and mouse IL-12p40 in vivo antagonism in the skin of DITRA-like mice.
  • Fig. S8. Anti–hIL-36R antibody prophylactic treatment suppresses mouse IL-23–induced epidermal hyperplasia in DITRA-like mice.
  • Fig. S9. Acute and chronic IMQ-induced skin inflammation in DITRA-like mice.
  • Fig. S10. Differential transcriptional changes induced by mouse IL-36α, mouse IL-36β, and mouse IL-36γ overexpression in vivo.
  • Fig. S11. DITRA-like mice display shortened colons at the age of 3 and 10 months at steady state.
  • Fig. S12. Expression of members of IL-36 family in DITRA-like and WT mice at steady state and in the setting of DSS-induced colitis.
  • Fig. S13. Frequency of myeloid populations in the colon lamina propria of DITRA-like, IL-36R KO, and WT mice at steady state.
  • Fig. S14. DITRA-like mice exhibit increased mortality rate in the recovery phase of DSS-induced colitis.
  • Fig. S15. Myeloid cell infiltration in the colon lamina propria of DSS-treated DITRA-like and WT mice.
  • Fig. S16. Therapeutic administration of recombinant IL-22 leads to recovery of DITRA-like mice from DSS-induced mucosal damage.
  • Fig. S17. Increased mRNA and protein levels of IL-36 cytokines in the colon of DITRA-like mice at steady state.
  • Fig. S18. IL-36R deficiency reduces DSS-induced acute colitis and does not alter the recovery in the repair phase of the disease.
  • Fig. S19. Comparable inhibition of DSS transcriptional signature with hIL-36R and mouse IL-12p40 in vivo antagonism in the colon of DITRA-like mice.
  • Fig. S20. hIL-36R antagonism ameliorates oxazolone-induced colitis in DITRA-like mice in vivo.
  • Table S1. Mouse IL-36Ra inhibits hIL-36α, hIL-36β, and hIL-36γ 20-fold weaker than hIL-36Ra in bioassays in vitro.
  • References (83, 84)

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Other Supplementary Material for this manuscript includes the following:

  • Table S2. Molecular profiling data (Excel spreadsheet).
  • Table S3. Genes induced by IL-36α and IL-36β in intestinal tissue after hydrodynamic DNA delivery (Excel spreadsheet).
  • Table S4. Raw data file (Excel spreadsheet).