These authors contributed equally to the work.
Version of Record online: 4 DEC 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 1, pages 351–361, January 2013
How to Cite
Loi, P., Yuan, Q., Torres, D., Delbauve, S., Laute, M.-A., Lalmand, M.-C., Pétein, M., Goriely, S., Goldman, M. and Flamand, V. (2013), Interferon regulatory factor 3 deficiency leads to interleukin-17-mediated liver ischemia-reperfusion injury. Hepatology, 57: 351–361. doi: 10.1002/hep.26022
Potential conflict of interest: Nothing to report.
The Institute for Medical Immunology is sponsored by the government of the Walloon Region and GlaxoSmithKline Biologicals. This study was also supported by the Fonds National de la Recherche Scientifique (FNRS, Belgium) and an Interuniversity Attraction Pole of the Belgian Federal Science Policy. P.L. is supported by Roche grants.
- Issue online: 7 JAN 2013
- Version of Record online: 4 DEC 2012
- Accepted manuscript online: 22 AUG 2012 03:22AM EST
- Manuscript Accepted: 1 AUG 2012
- Manuscript Received: 9 MAR 2012
Additional Supporting Information may be found in the online version of this article.
|HEP_26022_sm_SuppFig1.tif||18285K||Figure 1S. Liver pathology after two-lobe liver IR. A. Representative sample of at least 10 mice per each group (wild type, IRF3-/- and TRIF-/- mice), showing the ischemic lobes immediately after harvest. B. Liver lobe and HE stained liver section (1 ×) and C. liver section (40 ×, and 100 × original magnification) from representative sample of 10 Sham-treated mice. D. Score of necrosis, vacuolization and congestion from Sham and IR WT, IRF3-/- and TRIF-/- mice at 48h. * p < 0.05|
|HEP_26022_sm_SuppFig2.tif||9277K||Figure 2S. Serum aminotransferase measurement, liver pathology and scoring after one-lobe liver IR. A. Serum ALT levels in wild type and IRF3-/- mice after partial ischemia (one-lobe 90-min) and 4, 20 or 48 hours reperfusion. Sham controls displayed blood sample at 4 hours after reperfusion. Results are mean values ± SEM (n = 7-13). B. Scoring of the ischemic liver sections according to the Suzuki's criteria, showing the score of necrosis. C. Representative sample of anti-Ly-6G immunostaining on 20h or 48h post-IR and Sham liver section from wild type and IRF3-/- mice (40 × original magnification). (* p < 0.05, ** p < 0.01, *** p < 0.001).|
|HEP_26022_sm_SuppFig4.tif||7335K||Figure 4S. A. Control liver histology after IL-17A neutralization. IL-17 and Ly-6G rat IgG controls plus biotin-conjugated anti-rat IgG immunostaining on control Ig and anti-IL17A mAb treated WT or IRF3-/- mice 48h post liver IR. Sections are representative of 8 independent mice per experimental group (40 x original magnification). B. MPO activity in the liver tissue 48h after I/R in 6 Sham mice, 9 control IgG-treated IR mice and 4 anti-IL-17 or anti-Ly-6G/C-treated IR mice. * p < 0.05, ** p < 0.01,|
|HEP_26022_sm_SuppFig5.tif||9888K||Figure 5S. A. Hepatic IL-23p40 mRNA contents after TLR4 engagement. Low density fraction, F4/80+ purified or CD11c+ purified cells were collected from the liver or the spleen of C57BL/6 wild type or IRF3-/- mice that were i.v. injected with vehicle (sham) or LPS 2 hours before. mRNA were extracted from a pool of 4 mice per experimental group and analyzed by real-time RT-PCR. IL-12p40 mRNA contents were normalized using ?-actin mRNA as reference. Results are mean values ± SEM and were collected from 4 independent experiments (* p < 0.05). B. Hepatic tissue IL-10, IL-1ra, TNF-a, IL-27p28 mRNA contents after TLR4 engagement. Liver fraction were collected from WT and IRF3-/- mice 1h30 and 3h after LPS treatment. Data are expressed as 5 independent mRNA relative units compared with the value obtained in the respective untreated mice (n=5). * p < 0.05.NS, non significant.|
|HEP_26022_sm_SuppFig6.tif||154K||Figure 6S. IL-27p28 and IL-23 producing M1 type liver macrophages. Liver low density fraction were stained for F4/80, CD11c, TNF-?, IL-10, IL-27p28 and IL-23p19 after in vitro LPS treatment. Data are mean percentages ± SEM from 20 WT and IRF3-/- mice collected in 3 independent experiments for F4/80+ CD11c- cells (A) and TFN-?high IL-10low producing cells (B). C. Representative percentage of IL-27p28 and IL-23p19 producing M1 type macrophage out of 3 experiments.|
|HEP_26022_sm_SuppFig7.tif||2871K||Figure 7S. IL-17A producing cells in the liver and the spleen after TLR4 engagement. A. Mononuclear cells were isolated from the liver or the spleen of a pool of 5 C57BL/6 wild type or IRF3-/- mice stimulated as described. IL-17A and IFN-? secreting cells were measured by FACS. Numbers indicated the percentage of positively stained among TCR?? T cells or CD3+ NK1.1+ gated cells. The results are representative of 3 independent experiments. B. Fold induction of liver IL-17 producing cells in LPS or vehicule treated WT or IRF3-/- mice. Mean values of induction compared to vehicle treated mice in each strain; p value are calculated with a t-test. * p < 0.05.|
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