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IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models

Non-alcoholic fatty liver disease (NAFLD), represents an unmet medical need that can progress to non-alcoholic steatohepatitis (NASH), which, without intervention, can result in the development of cirrhosis and hepatocellular carcinoma (HCC). Inflammation is a pathological hallmark of NASH, and targ...

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Autores principales: Heredia, Jose E., Sorenson, Clara, Flanagan, Sean, Nunez, Victor, Jones, Charles, Martzall, Angela, Leong, Laurie, Martinez, Andres Paler, Scherl, Alexis, Brightbill, Hans D., Ghilardi, Nico, Ding, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9477333/
https://www.ncbi.nlm.nih.gov/pubmed/36107926
http://dx.doi.org/10.1371/journal.pone.0274582
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author Heredia, Jose E.
Sorenson, Clara
Flanagan, Sean
Nunez, Victor
Jones, Charles
Martzall, Angela
Leong, Laurie
Martinez, Andres Paler
Scherl, Alexis
Brightbill, Hans D.
Ghilardi, Nico
Ding, Ning
author_facet Heredia, Jose E.
Sorenson, Clara
Flanagan, Sean
Nunez, Victor
Jones, Charles
Martzall, Angela
Leong, Laurie
Martinez, Andres Paler
Scherl, Alexis
Brightbill, Hans D.
Ghilardi, Nico
Ding, Ning
author_sort Heredia, Jose E.
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD), represents an unmet medical need that can progress to non-alcoholic steatohepatitis (NASH), which, without intervention, can result in the development of cirrhosis and hepatocellular carcinoma (HCC). Inflammation is a pathological hallmark of NASH, and targeting key inflammatory mediators of NASH may lead to potential therapeutics for the disease. Herein, we aimed to investigate the role of IL-23 signaling in NASH progression in murine models. We showed that recombinant IL-23 can promote IL-17 producing cell expansion in the liver and that these cells are predominately γδ T cells and Mucosal Associated Invariant T cells (MAITs). Reciprocally, we found that IL-23 signaling is necessary for the expansion of γδ T cells and MAIT cells in the western diet (WD) diet induced NASH model. However, we did not observe any significant differences in liver inflammation and fibrosis between wild type and Il23r-/- mice in the same NASH model. Furthermore, we found that Il23r deletion does not impact liver inflammation and fibrosis in the choline-deficient, L-amino acid-defined and high-fat diet (CDA-HFD) induced NASH model. Based on these findings, we therefore propose that IL-23 signaling is not necessary for NASH pathogenesis in preclinical models and targeting this pathway alone may not be an effective therapeutic approach to ameliorate the disease progression in NASH patients.
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spelling pubmed-94773332022-09-16 IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models Heredia, Jose E. Sorenson, Clara Flanagan, Sean Nunez, Victor Jones, Charles Martzall, Angela Leong, Laurie Martinez, Andres Paler Scherl, Alexis Brightbill, Hans D. Ghilardi, Nico Ding, Ning PLoS One Research Article Non-alcoholic fatty liver disease (NAFLD), represents an unmet medical need that can progress to non-alcoholic steatohepatitis (NASH), which, without intervention, can result in the development of cirrhosis and hepatocellular carcinoma (HCC). Inflammation is a pathological hallmark of NASH, and targeting key inflammatory mediators of NASH may lead to potential therapeutics for the disease. Herein, we aimed to investigate the role of IL-23 signaling in NASH progression in murine models. We showed that recombinant IL-23 can promote IL-17 producing cell expansion in the liver and that these cells are predominately γδ T cells and Mucosal Associated Invariant T cells (MAITs). Reciprocally, we found that IL-23 signaling is necessary for the expansion of γδ T cells and MAIT cells in the western diet (WD) diet induced NASH model. However, we did not observe any significant differences in liver inflammation and fibrosis between wild type and Il23r-/- mice in the same NASH model. Furthermore, we found that Il23r deletion does not impact liver inflammation and fibrosis in the choline-deficient, L-amino acid-defined and high-fat diet (CDA-HFD) induced NASH model. Based on these findings, we therefore propose that IL-23 signaling is not necessary for NASH pathogenesis in preclinical models and targeting this pathway alone may not be an effective therapeutic approach to ameliorate the disease progression in NASH patients. Public Library of Science 2022-09-15 /pmc/articles/PMC9477333/ /pubmed/36107926 http://dx.doi.org/10.1371/journal.pone.0274582 Text en © 2022 Heredia et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Heredia, Jose E.
Sorenson, Clara
Flanagan, Sean
Nunez, Victor
Jones, Charles
Martzall, Angela
Leong, Laurie
Martinez, Andres Paler
Scherl, Alexis
Brightbill, Hans D.
Ghilardi, Nico
Ding, Ning
IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title_full IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title_fullStr IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title_full_unstemmed IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title_short IL-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
title_sort il-23 signaling is not an important driver of liver inflammation and fibrosis in murine non-alcoholic steatohepatitis models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9477333/
https://www.ncbi.nlm.nih.gov/pubmed/36107926
http://dx.doi.org/10.1371/journal.pone.0274582
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