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Cells
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Molecular Mechanism of Autoimmune Hepatitis and Biliary Cholangiopathy
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Molecular Mechanism of Autoimmune Hepatitis and Biliary Cholangiopathy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 8408

Special Issue Editor

Dr. Fabrizio Bronte

E-Mail Website
Guest Editor
Ospedali Riuniti Villa Sofia-V. Cervello, Università degli Studi di Palermo, Palermo, Italy
Interests: liver and biliary cancer; hepatitis; autoimmune
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, hepatology has undergone a significant development thanks to the introduction of direct-acting antiviral therapy (DAA). This will lead to the complete eradication of hepatitis C virus (HCV). Now, particular attention is being paid to autoimmune hepatitis and autoimmune cholangiopathies which, together with non-alcoholic steato-hepatitis (NASH), will represent the major cause of cirrhosis and its complications in the near future. This Special Issue will focus on the molecular mechanisms that underlie these autoimmune diseases—their development, progression, and complications—to hopefully identify specific molecular targets for their treatment. 

Dr. Fabrizio Bronte
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Autoimmune Hepatitis
  • Liver
  • Biliary cholangiopathy
  • Molecular mechanism
  • Cirrhosis
  • Treatment

Published Papers (3 papers)

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Research

11 pages, 2184 KiB  
Article
Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease
by Zuzana Macek Jilkova, Marie Noelle Hilleret, Theophile Gerster, Nathalie Sturm, Marion Mercey-Ressejac, Jean-Pierre Zarski, Vincent Leroy, Patrice N. Marche, Charlotte Costentin and Thomas Decaens
Cells 2021, 10(10), 2671; https://doi.org/10.3390/cells10102671 - 06 Oct 2021
Cited by 6 | Viewed by 2212
Abstract
Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis [...] Read more.
Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis (AIH). Here, we performed a multiparametric analysis of ICM, including PD-1, TIM3, LAG3, CTLA-4, OX40 and 4-1BB, and we determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with AIH in comparison to normal liver tissue. AIH patient-derived liver tissue revealed the overexpression of ICM, mainly PD-1 and 4-1BB, as well as the strong correlation between PD-1+ CD8+ T-cell abundance and severity of AIH (alanine transaminase and aspartate transaminase levels). Our results show that the ICM play an important role in the loss of immune homeostasis in the liver, providing an attractive approach to investigate their role as targets for effective therapeutic interventions. Full article
(This article belongs to the Special Issue Molecular Mechanism of Autoimmune Hepatitis and Biliary Cholangiopathy)
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23 pages, 5276 KiB  
Article
Familiarity Breeds Strategy: In Silico Untangling of the Molecular Complexity on Course of Autoimmune Liver Disease-to-Hepatocellular Carcinoma Transition Predicts Novel Transcriptional Signatures
by Soumyadeep Mukherjee, Arpita Kar, Najma Khatun, Puja Datta, Avik Biswas and Subhasis Barik
Cells 2021, 10(8), 1917; https://doi.org/10.3390/cells10081917 - 29 Jul 2021
Cited by 7 | Viewed by 3120
Abstract
Autoimmune liver diseases (AILD) often lead to transformation of the liver tissues into hepatocellular carcinoma (HCC). Considering the drawbacks of surgical procedures in such cases, need of successful non-invasive therapeutic strategies and treatment modalities for AILD-associated-HCC still exists. Due to the lack of [...] Read more.
Autoimmune liver diseases (AILD) often lead to transformation of the liver tissues into hepatocellular carcinoma (HCC). Considering the drawbacks of surgical procedures in such cases, need of successful non-invasive therapeutic strategies and treatment modalities for AILD-associated-HCC still exists. Due to the lack of clear, sufficient knowledge about factors mediating AILD-to-HCC transition, an in silico approach was adopted to delineate the underlying molecular deterministic factors. Parallel enrichment analyses on two different public microarray datasets (GSE159676 and GSE62232) pinpointed the core transcriptional regulators as key players. Correlation between the expression kinetics of these transcriptional modules in AILD and HCC was found to be positive primarily with the advancement of hepatic fibrosis. Most of the regulatory interactions were operative during early (F0–F1) and intermediate fibrotic stages (F2–F3), while the extent of activity in the regulatory network considerably diminished at late stage of fibrosis/cirrhosis (F4). Additionally, most of the transcriptional targets with higher degrees of connectivity in the regulatory network (namely DCAF11, PKM2, DGAT2 and BCAT1) may be considered as potential candidates for biomarkers or clinical targets compared to their low-connectivity counterparts. In summary, this study uncovers new possibilities in the designing of novel prognostic and therapeutic regimen for autoimmunity-associated malignancy of liver in a disease progression-dependent fashion. Full article
(This article belongs to the Special Issue Molecular Mechanism of Autoimmune Hepatitis and Biliary Cholangiopathy)
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14 pages, 2611 KiB  
Article
Anti-CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively towards Regeneration
by Laura Elisa Buitrago-Molina, Janine Dywicki, Fatih Noyan, Lena Schepergerdes, Julia Pietrek, Maren Lieber, Jerome Schlue, Michael P. Manns, Heiner Wedemeyer, Elmar Jaeckel and Matthias Hardtke-Wolenski
Cells 2021, 10(6), 1471; https://doi.org/10.3390/cells10061471 - 11 Jun 2021
Cited by 9 | Viewed by 2167
Abstract
Background: Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of [...] Read more.
Background: Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term. Methods: We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease. Results: After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration. Conclusions: In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH. Full article
(This article belongs to the Special Issue Molecular Mechanism of Autoimmune Hepatitis and Biliary Cholangiopathy)
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