首页|Regulatory Effect of JAK2/STAT3 on the Immune Function of Endotoxin-tolerant Dendritic Cells and its Involvement in Acute Liver Failure
Regulatory Effect of JAK2/STAT3 on the Immune Function of Endotoxin-tolerant Dendritic Cells and its Involvement in Acute Liver Failure
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NETL
NSTL
万方数据
维普
Background and Aims: Acute liver failure (ALF) is a poten-tially fatal clinical syndrome with no effective treatment. This study aimed to explore the role of Janus kinase 2/signal trans-ducer and activator of transcription 3 (JAK2/STAT3) pathway in modulating the phenotype and immune function of en-dotoxin-tolerant dendritic cells (ETDCs). In addition, we ex-plored the use of EDTCs in an experimental model of ALF and investigated the associated mechanisms. Methods: In the in vitro experiment, ETDCs were transfected with adenovirus to induce SOCS1+/+ETDCs and SOCS1−/−ETDCs. Thereafter, costimulatory molecules and mixed lymphocyte reaction were assessed. Experimental mice were randomly divided into nor-mal control, ALF, ALF+mock-ETDCs, ALF+SOCS1+/+ETDCs, ALF+AG490, and ALF+AG490+SOCS1+/+ETDCs groups. We examined the therapeutic effect of adoptive cellular immuno-therapy by tail-vein injection of target ETDCs 12 h before ALF modeling. AG490, a JAK2/STAT3 inhibitor, was used in the in vivo experiment to further explore the protective mechanism of SOCS1+/+ETDCs. Results: Compared with control ETDCs, SOCS1+/+ETDCs had lower expression of costimulatory mol-ecules, weaker allostimulatory ability, lower levels of IL-6 and TNF-α expression and higher IL-10 secretion. SOCS1−/−ETDCs showed the opposite results. In the in vivo experiments, the ALF+SOCS1+/+ETDCs and ALF+AG490+SOCS1+/+ETDCs groups showed less pathological damage and suppressed activation of JAK2/STAT3 pathway. The changes were more pronounced in the ALF+AG490+SOCS1+/+ETDCs group. In-fusion of SOCS1+/+ETDCs had a protective effect against ALF possibly via inhibition of JAK2 and STAT3 phosphorylation. Conclusions: The SOCS1 gene had an important role in in-duction of endotoxin tolerance. SOCS1+/+ETDCs alleviated lipopolysaccharide/D-galactosamine-induced ALF by down-regulating the JAK2/STAT3 signaling pathway.
Liver failureAcuteJanus kinase 2/signal transducers and activa-tors of transcription 3 (JAK2/STAT3)Endotoxin toleranceDendritic cells
NETL
NSTL
万方数据
维普
