Open AccessBone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis
Author(s) -
Takeru Amiya,
Nobuhiro Nakamoto,
Po–Sung Chu,
Toshiaki Teratani,
Hideaki Nakajima,
Yumi Fukuchi,
Nobuhito Taniki,
Akihiro Yamaguchi,
Shintaro Shiba,
Rei Miyake,
Tadashi Katayama,
Hirotoshi Ebinuma,
Takanori Kanai
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35146
Subject(s) - liver injury , bone marrow , chimera (genetics) , integrin alpha m , hepatic stellate cell , concanavalin a , immunology , macrophage , pathology , medicine , cancer research , biology , microbiology and biotechnology , immune system , in vitro , biochemistry , gene
The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9 + inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9 + Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11b low F4/80 high hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9 + Mφs were firmly replaced by donors, indicating that CCR9 + Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU + CCR9 + Mφs 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 Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury.