Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.
Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.
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DOI：
10.1002/hep.26267
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发表时间：
2013-08
期刊：
影响因子：
13.5
通讯作者：
Miller, George
中科院分区：
文献类型：
--
作者：
Henning, Justin R.;Graffeo, Christopher S.;Rehman, Adeel;Fallon, Nina C.;Zambirinis, Constantinos P.;Ochi, Atsuo;Barilla, Rocky;Jamal, Mohsin;Deutsch, Michael;Greco, Stephanie;Ego-Osuala, Melvin;Bin-Saeed, Usama;Rao, Raghavendra S.;Badar, Sana;Quesada, Juan P.;Acehan, Devrim;Miller, George
非酒精性脂肪性肝炎（NASH）是美国慢性肝功能障碍的最常见病因，可进展为肝硬化和肝功能衰竭。肝脏脂肪浸润引起的炎症损伤是疾病发病机制的核心。树突状细胞（DC）是一种抗原提呈细胞，在肝脏炎症中发挥着重要作用。我们推测DC在NASH的进展中是重要的。我们发现肝内DC在NASH肝脏中扩增和成熟，并呈现活化的免疫表型。然而，DC耗竭不仅没有减轻NASH的严重程度，反而显著加剧了肝内纤维炎症。我们的机制研究支持DC在NASH中的调节作用，通过其在清除凋亡细胞和坏死碎片中的作用限制无菌炎症。我们发现DC限制了CD8+ T细胞的扩增，并限制了NASH中先天免疫效应细胞（包括枯否细胞、中性粒细胞和炎性单核细胞）中Toll样受体的表达和细胞因子的产生。与它们在NASH中的调节作用一致，在疾病的恢复阶段，DC群的消融导致肝内炎症和纤维组织增生的延迟消退。我们的研究结果支持DC在调节NASH中的作用。靶向DC功能特性可能有望用于NASH的治疗干预。
Non-alcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DC) are antigen presenting cells with an emerging role in hepatic inflammation. We postulated that DC are important in the progression of NASH. We found that intrahepatic DC expand and mature in NASH liver and assume an activated immune-phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibro-inflammation. Our mechanistic studies support a regulatory role for DC in NASH by limiting sterile inflammation via their role in clearance of apoptotic cells and necrotic debris. We found that DC limit CD8+ T cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Our findings support a role for DC in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH.
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影响因子：
29.4
作者：
Miura K;Kodama Y;Inokuchi S;Schnabl B;Aoyama T;Ohnishi H;Olefsky JM;Brenner DA;Seki E
通讯作者：
Seki E
DOI：
10.1164/rccm.200907-1164oc
发表时间：
2010-08-01
影响因子：
24.7
作者：
Bantsimba-Malanda, Claudie;Marchal-Somme, Joelle;Soler, Paul
通讯作者：
Soler, Paul
影响因子：
5.4
作者：
Jomantaite, L;Dikopoulos, N;Reimann, J
通讯作者：
Reimann, J
影响因子：
4.2
作者：
Lu, Lawrence;Faubel, Sarah;Edelstein, Charles L.
通讯作者：
Edelstein, Charles L.
影响因子：
13.5
作者：
POWELL, EE;COOKSLEY, WGE;POWELL, LW
通讯作者：
POWELL, LW