Splenic CD11c(low)CD45RB(high) dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure.
Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Sai-Nan
SN
Zhang
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Nai-Bin
NB
Yang
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Shun-Lan
SL
Ni
Department of Intensive Care Unit, The First Hospital of Ningbo, Ningbo 315010, Zhejiang, P. R. China.
Jin-Zhong
JZ
Dong
Department of Infection Diseases, The First Hospital of Xiaoshan, Hangzhou 311200, Zhejiang, P. R. China.
Chun-Wei
CW
Shi
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Shan-Shan
SS
Li
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Sheng-Guo
SG
Zhang
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Xin-Yue
XY
Tang
Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang, P. R. China.
Ming-Qin
MQ
Lu
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D060467:Disease Resistance; D017493:Leukocyte Common Antigens / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology* / Q000473:pathology
D039521:CD11c Antigen; D016207:Cytokines; D008070:Lipopolysaccharides; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse