Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis

Takeru Amiya, Nobuhiro Nakamoto, Po Sung Chu, Toshiaki Teratani, Hideaki Nakajima, Yumi Fukuchi, Nobuhito Taniki, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Hirotoshi Ebinuma, Takanori Kanai

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10 Citations (Scopus)

Abstract

The fundamental mechanism how heterogeneous hepatic macrophage (MÏ †) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9 + inflammatory M†s play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9 + M†s, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident M †s. First, irradiated mice developed less liver injury with less M†s accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11blowF4/80high hepatic-resident M†s were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9 + M†s were firmly replaced by donors, indicating that CCR9 + M†s originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU + CCR9 + M†s with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b + cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory M†s originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury.

Original languageEnglish
Article number35146
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Oct 11

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