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 language | English |
|---|---|
| Article number | 35146 |
| Journal | Scientific Reports |
| Volume | 6 |
| DOIs | |
| Publication status | Published - 2016 Oct 11 |
Fingerprint
ASJC Scopus subject areas
- General
Cite this
Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis. / Amiya, Takeru; Nakamoto, Nobuhiro; Cho, Hakusyo; Teratani, Toshiaki; Nakajima, Hideaki; Fukuchi, Yumi; Taniki, Nobuhito; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ebinuma, Hirotoshi; Kanai, Takanori.
In: Scientific Reports, Vol. 6, 35146, 11.10.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis
AU - Amiya, Takeru
AU - Nakamoto, Nobuhiro
AU - Cho, Hakusyo
AU - Teratani, Toshiaki
AU - Nakajima, Hideaki
AU - Fukuchi, Yumi
AU - Taniki, Nobuhito
AU - Yamaguchi, Akihiro
AU - Shiba, Shunsuke
AU - Miyake, Rei
AU - Katayama, Tadashi
AU - Ebinuma, Hirotoshi
AU - Kanai, Takanori
PY - 2016/10/11
Y1 - 2016/10/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991340916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991340916&partnerID=8YFLogxK
U2 - 10.1038/srep35146
DO - 10.1038/srep35146
M3 - Article
C2 - 27725760
AN - SCOPUS:84991340916
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 35146
ER -