Figure 6
Figure 6. Nlrp3 deficiency and either miR-155 antagonism or miR-155 deficiency display no synergy in protection from GVHD. (A) Mice received an allo-HCT (BALB/c → WT or Nlrp3−/− C57BL/6) and were treated with nonfunctional antagomir-control or functional antagomir-155 on days 0, 3, and 9 after allo-HCT. Survival was monitored for 100 days. The experiment was performed twice (n = 11-14/group; P < .0001 for WT recipients, no significant difference observed for Nlrp3−/− recipients). (B) Organs of the recipients that had survived in (A) until day 100 were isolated, and paraffin sections of the small intestine, large intestine, and liver were stained with hematoxylin and eosin. Histopathology scoring was performed as described. The experiment was performed twice (n = 7-9/group, no significant difference observed between Nlrp3−/− recipients treated with antagomir-control and antagomir-155). (C) Lethally irradiated WT C57BL/6 mice were transplanted with 5 × 106 BM cells from a syngeneic Nlrp3−/− or Nlrp3/miR-155 DKO C57BL/6 donor. After 30 days, the BM chimeric mice were irradiated with 5 Gy and injected with 5 × 106 BM cells and 8 × 105 CD4+/CD8+ T cells from an allogeneic BALB/c donor. Survival data were pooled from 2 independent experiments (n = 14-15/group, no significant difference between the groups). (D) Organs of the recipients that had survived in (C) until day 100 were isolated, and paraffin sections of the small intestine, large intestine, and liver were stained with hematoxylin and eosin. Histopathology scoring was performed as described (n = 9/group, no significant difference observed between Nlrp3−/− and Nlrp3/miR-155 DKO BM chimeric mice). (E) Lethally irradiated WT C57BL/6 mice were transplanted with 5 × 106 BM cells from a syngeneic Nlrp3/miR-155 DKO C57BL/6 donor. After 30 days, the Nlrp3/miR-155 DKO BM chimeric mice were irradiated with 5 Gy and injected with 5 × 106 BM cells and 8 × 105 CD4+/CD8+ T cells from an allogeneic BALB/c donor. Groups additionally received 2 × 106 miR-155−/− or Nlrp3/miR-155 DKO C57BL/6 BM-derived DCs on the day of allo-HCT (n = 10/group).

Nlrp3 deficiency and either miR-155 antagonism or miR-155 deficiency display no synergy in protection from GVHD. (A) Mice received an allo-HCT (BALB/c → WT or Nlrp3−/− C57BL/6) and were treated with nonfunctional antagomir-control or functional antagomir-155 on days 0, 3, and 9 after allo-HCT. Survival was monitored for 100 days. The experiment was performed twice (n = 11-14/group; P < .0001 for WT recipients, no significant difference observed for Nlrp3−/− recipients). (B) Organs of the recipients that had survived in (A) until day 100 were isolated, and paraffin sections of the small intestine, large intestine, and liver were stained with hematoxylin and eosin. Histopathology scoring was performed as described. The experiment was performed twice (n = 7-9/group, no significant difference observed between Nlrp3−/− recipients treated with antagomir-control and antagomir-155). (C) Lethally irradiated WT C57BL/6 mice were transplanted with 5 × 106 BM cells from a syngeneic Nlrp3−/− or Nlrp3/miR-155 DKO C57BL/6 donor. After 30 days, the BM chimeric mice were irradiated with 5 Gy and injected with 5 × 106 BM cells and 8 × 105 CD4+/CD8+ T cells from an allogeneic BALB/c donor. Survival data were pooled from 2 independent experiments (n = 14-15/group, no significant difference between the groups). (D) Organs of the recipients that had survived in (C) until day 100 were isolated, and paraffin sections of the small intestine, large intestine, and liver were stained with hematoxylin and eosin. Histopathology scoring was performed as described (n = 9/group, no significant difference observed between Nlrp3−/− and Nlrp3/miR-155 DKO BM chimeric mice). (E) Lethally irradiated WT C57BL/6 mice were transplanted with 5 × 106 BM cells from a syngeneic Nlrp3/miR-155 DKO C57BL/6 donor. After 30 days, the Nlrp3/miR-155 DKO BM chimeric mice were irradiated with 5 Gy and injected with 5 × 106 BM cells and 8 × 105 CD4+/CD8+ T cells from an allogeneic BALB/c donor. Groups additionally received 2 × 106miR-155−/− or Nlrp3/miR-155 DKO C57BL/6 BM-derived DCs on the day of allo-HCT (n = 10/group).

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