期刊
HEPATOLOGY COMMUNICATIONS
卷 2, 期 3, 页码 329-343出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/hep4.1145
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资金
- Institut National de la Sante et de la Recherche Medicale
- Agence Nationale de la Recherche [ANR-09-RPDOC-016-01 HEPATICEL]
- Institut Universitaire de France
- French Ministry of Education and Research
- Universite Paris-Est-Creteil grants for young investigators
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [ZIAAA000368, ZIAAA000369] Funding Source: NIH RePORTER
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)(+) LPCs, and both cell types colocalized and their numbers positively correlated with each other. The role of IL-17 in the induction of LPCs was examined in a mouse model fed a choline-deficient and ethionine-supplemented (CDE) diet. Feeding of wild-type mice with the CDE diet markedly elevated CK19(+)Ki67(+) proliferating LPCs and hepatic inflammation. Disruption of the IL-17 gene or IL-27 receptor, alpha subunit (WSX-1) gene abolished CDE diet-induced LPC expansion and inflammation. In vitro treatment with IL-17 promoted proliferation of bipotential murine oval liver cells (a liver progenitor cell line) and markedly upregulated IL-27 expression in macrophages. Treatment with IL-27 favored the differentiation of bipotential murine oval liver cells and freshly isolated LPCs into hepatocytes. Conclusion: The current data provide evidence for a collaborative role between IL-17 and IL-27 in promoting LPC expansion and differentiation, respectively, thereby contributing to liver regeneration.
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