CD11b+ Gr1+ bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice

Yang Gun Suh, Ja Kyung Kim, Jin Seok Byun, Hyon Seung Yi, Young Sun Lee, Hyuk Soo Eun, So Yeon Kim, Kwang Hyub Han, Kwan Sik Lee, Gregg Duester, Scott L. Friedman, Won Il Jeong

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


Clinical trials and animal models suggest that infusion of bone marrow cells (BMCs) is effective therapy for liver fibrosis, but the underlying mechanisms are obscure, especially those associated with early effects of BMCs. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMCs showing antifibrotic effects in mice with carbon tetrachloride-induced liver fibrosis. An interaction between BMCs and activated hepatic stellate cells (HSCs) was investigated using an in vitro coculturing system. Within 24 hours, infused BMCs were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, and expanded regulatory T cells but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10-deficient (IL-10-/-) BMCs failed to reproduce these effects in fibrotic livers. Intriguingly, in isolated cells, CD11b+Gr1highF4/80- and CD11b+Gr1+F4/80+ BMCs expressed more IL-10 after coculturing with activated HSCs, leading to suppressed expression of collagen and α-smooth muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMCs were cocultured with IL-6-/- and retinaldehyde dehydrogenase 1-/- HSCs. Similar to murine data, human BMCs expressed more IL-10 after coculturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion. Conclusion: Activated HSCs increase IL-10 expression in BMCs (CD11b+Gr1highF4/80- and CD11b+Gr1+F4/80+ cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis.

Original languageEnglish
Pages (from-to)1902-1912
Number of pages11
Issue number5
Publication statusPublished - 2012 Nov

ASJC Scopus subject areas

  • Hepatology


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