Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/175454
Title: The role of macrophage-inducible C-type lectin in different stages of chronic liver disease
Author: Schierwagen, Robert
Uschner, Frank E.
Ortiz, Cristina
Torres, Sandra
Brol, Max J.
Tyc, Olaf
Gu, Wenyi
Grimm, Christian
Zeuzem, Stefan
Plamper, Andreas
Pfeifer, Philipp
Zimmer, Sebastian
Welsch, Christoph
Schaefer, Liliana
Rheinwalt, Karl P.
Clària i Enrich, Joan
Arroyo, Vicente
Trebicka, Jonel
Klein, Sabine
Keywords: Malalties del fetge
Fibrosi quística
Inflamació
Liver diseases
Cystic fibrosis
Inflammation
Issue Date: 7-Jul-2020
Publisher: Frontiers Media
Abstract: The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.
Note: Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.01352
It is part of: Frontiers in Immunology, 2020, vol. 11, p. 1352
URI: http://hdl.handle.net/2445/175454
Related resource: https://doi.org/10.3389/fimmu.2020.01352
ISSN: 1664-3224
Appears in Collections:Articles publicats en revistes (Biomedicina)

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