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Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice
Author(s) -
Henning Justin R.,
Graffeo Christopher S.,
Rehman Adeel,
Fallon Nina C.,
Zambirinis Constantinos P.,
Ochi Atsuo,
Barilla Rocky,
Jamal Mohsin,
Deutsch Michael,
Greco Stephanie,
EgoOsuala Melvin,
BinSaeed Usama,
Rao Raghavendra S.,
Badar Sana,
Quesada Juan P.,
Acehan Devrim,
Miller George
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26267
Subject(s) - nonalcoholic steatohepatitis , limit (mathematics) , steatohepatitis , medicine , nonalcoholic fatty liver disease , mathematics , fatty liver , disease , mathematical analysis
Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen‐presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8 + T‐cell expansion and restrict Toll‐like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion : Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. (H EPATOLOGY 2013;58:589–602)

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