CCR9+ macrophages are required for acute liver inflammation in mouse models of hepatitis

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Item Type:	Article
Title:	CCR9+ macrophages are required for acute liver inflammation in mouse models of hepatitis
Creators Name:	Nakamoto, N., Ebinuma, H., Kanai, T., Chu, P.S., Ono, Y., Mikami, Y., Ojiro, K., Lipp, M., Love, P.E., Saito, H. and Hibi, T.
Abstract:	BACKGROUND & AIMS: Antigen-presenting cells (APCs) are involved in the induction of liver inflammation. We investigated the roles of specific APCs in the pathogenesis of acute liver injury in mice. METHODS: We used concanavalin A (con A) or carbon tetrachloride to induce acute liver inflammation in mice and studied the roles of macrophages that express CCR9. RESULTS: After injection of con A, we detected CCR9(+)CD11b(+)CD11c(-) macrophages that express tumor necrosis factor (TNF)-alpha in livers of mice, whereas CCR9(+)Siglec-H(+)CD11b(-)CD11c(low) plasmacytoid DCs (pDCs), which are abundant in normal livers, disappeared. The CCR9(+) macrophages were also detected in the livers of RAG-2(-/-) mice, which lack lymphocytes and natural killer T cells, after injection of con A. Under inflammatory conditions, CCR9(+) macrophages induced naive CD4(+) T cells to become interferon gamma-producing Th1 cells in vivo and in vitro. CCR9(-/-) mice injected with con A did not develop hepatitis unless they also received CCR9(+) macrophages from mice that received con A; more CCR9(+) macrophages accumulated in their inflamed livers than CCR9(+) pDCs, CCR9(-) pDCs, or CCR9(-) macrophages isolated from mice that had received injections of con A. Levels of CCL25 messenger RNA increased in livers after injection of con A; neutralizing antibodies against CCL25 reduced the induction of hepatitis by con A by blocking the migration of CCR9(+) macrophages and their production of TNF-alpha. Peripheral blood samples from patients with acute hepatitis had greater numbers of TNF-alpha-producing CCR9(+)CD14(+)CD16(high) monocytes than controls. CONCLUSIONS: CCR9(+) macrophages contribute to the induction of acute liver inflammation in mouse models of hepatitis.
Keywords:	Immune Regulation, Hepatic Disease, Chemokine Receptor, T-Cell Activation, Animals, Mice
Source:	Gastroenterology
ISSN:	0016-5085
Publisher:	Elsevier / Saunders
Volume:	142
Number:	2
Page Range:	366-376
Date:	February 2012
Official Publication:	https://doi.org/10.1053/j.gastro.2011.10.039
PubMed:	View item in PubMed

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