These authors contributed equally to this work.
Autoimmune, Cholestatic and Biliary Disease
Genetic predisposition and environmental danger signals initiate chronic autoimmune hepatitis driven by CD4+ T cells
Version of Record online: 1 JUL 2013
Copyright © 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 2, pages 718–728, August 2013
How to Cite
Hardtke-Wolenski, M., Fischer, K., Noyan, F., Schlue, J., Falk, C. S., Stahlhut, M., Woller, N., Kuehnel, F., Taubert, R., Manns, M. P. and Jaeckel, E. (2013), Genetic predisposition and environmental danger signals initiate chronic autoimmune hepatitis driven by CD4+ T cells. Hepatology, 58: 718–728. doi: 10.1002/hep.26380
Potential conflict of interest: Nothing to report.
Supported by grants from the German Research Foundation (KFO250 project 7) and the cluster of excellence REBIRTH.
- Issue online: 29 JUL 2013
- Version of Record online: 1 JUL 2013
- Accepted manuscript online: 8 MAR 2013 11:28AM EST
- Manuscript Accepted: 1 MAR 2013
- Manuscript Received: 31 OCT 2012
Additional Supporting Information may be found in the online version of this article.
|hep26380-sup-0001-suppfig1.tif||8119K||Supporting Figure 1 Adenoviral constructs with eGFP and human FTCD led to expression in hepatoma cells latter is recognized by sera of AIH patients (A) Human FTCD, murine FTCD and control eGFP were cloned in a replication-deficient Adenovirus (Ad5). The vector map of AdEasy-1-hFTCD is shown. (B) Western blots of Ad-hFTCD transduced 293 (left panel) or HepG2 (right panel) cells. The expression of human FTCD was verified with a representative anti-LC1-positive human serum (LC1) and a representative normal donor serum (ND).|
|hep26380-sup-0002-suppfig2.tif||2224K||Supporting Figure 2 Adenoviral cleaning in the liver within the first weeks after infection PCR for adenovirus were performed of hepatic DNA of Ad-eGFP (n=6), Ad-hFTCD (n=11) infected NOD mice at week 12, plasmid DNA of Ad-hFTCD (+) and water control (-).|
|hep26380-sup-0003-suppfig3.tif||2850K||Supporting Figure 3 pIRES-eGFP-mFTCD with myc-tag led to expression in hepatoma cells Western blot of 293 cells transfected with pIRES-eGFP-mFTCD (right lanes) or control pIRES-eGFP transfected 293 cells (left lanes). The 58.8 kD FTCD construct was detected by an anti-myc-tag antibody (left panel) or a representative serum from an Ad-hFTCD infected NOD mouse (right panel).|
|hep26380-sup-0004-suppfig4.tif||4603K||Supporting Figure 4 Massive hepatic infiltrations and fibrosis in Ad-hFTCD infected mice (A) Liver sections were quantitative analyzed at week 12 using the average size of intrahepatic infiltrates. (B) Representative H&E stainings of C57Bl/6 and FVB/N 12 weeks after Ad-hFTCD infection.|
|hep26380-sup-0005-suppfig5.tif||3928K||Supporting Figure 5 Additional characterization of IHLs Representative multi-lineage characterization of IHLs from Ad-hFTCD (n=9) infected mice via flow cytometry is shown. Indicated are the populations of the NK and CD3+ T cells (left panels) and the αβTCR and γδT cell populations (right panels).|
|hep26380-sup-0006-suppfig6.tif||4925K||Supporting Figure 6 Recombinant mFTCD and unaltered cytokine levels in sera of Ad-hFTCD infected NOD mice (A) Coomassie staining of recombinant mFTCD produced in BL21 and purified using Ni-NTA. (B) Cytokine analysis of sera from Ad-eGFP or Ad-hFTCD infected mice at week 12. Concentration (pg/ml) were determined by multiplex technology and mean values are shown (±SD) (n=10).|
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