Hepatic IL-17 responses in human and murine primary biliary cirrhosis.
Hepatic IL-17 responses in human and murine primary biliary cirrhosis.
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DOI：
10.1016/j.jaut.2008.11.001
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发表时间：
2009-02
影响因子：
12.8
通讯作者：
Gershwin ME
中科院分区：
文献类型：
--
作者：
Lan RY;Salunga TL;Tsuneyama K;Lian ZX;Yang GX;Hsu W;Moritoki Y;Ansari AA;Kemper C;Price J;Atkinson JP;Coppel RL;Gershwin ME
新的调节性和促炎性免疫细胞亚群和细胞因子的出现表明需要重新检查这些亚群在涉及免疫系统的各种疾病中的作用。IL-17最近被鉴定为参与许多自身免疫过程的关键细胞因子。然而，其在肝脏自身免疫性疾病中的作用仍不清楚。原发性胆汁性肝硬化（PBC）的组织学特征是受损胆管周围的自身反应性CD 4和CD 8 T细胞。CD 4 + T细胞是IL-17的主要来源，其构成独特的辅助性T细胞亚群（Th 17）。因此，我们开始以肝靶向方式确定IL-17在PBC的人和鼠模型中的作用。我们的数据表明，与健康肝脏相比，PBC患者和其他肝功能障碍患者的肝组织中IL-17+淋巴细胞浸润的频率增加。IL-2受体α敲除小鼠（最近发现的人PBC小鼠模型）也显示门脉束内IL-17阳性细胞的显著聚集，以及与外周相比肝脏中Th 17细胞的频率增加。有趣的是，来自正常C57 BL/6 J小鼠肝脏的CD 4 + T细胞相对于来自脾脏的CD 4 + T细胞也分泌更高水平的IL-17，表明肝脏组织中优先诱导Th 17细胞。重要的是，与单独的T细胞相比，脾CD 4 + T细胞和肝脏非实质细胞的C57 BL/6 J共培养物使IL-17产生增加约10倍，这表明在肝脏自身免疫和其他肝脏炎性疾病的情况下，肝脏微环境在Th 17诱导中的作用。
The emergence of new regulatory and pro-inflammatory immune cell subsets and cytokines dictates the need to re-examine the role of these subsets in various diseases involving the immune system. IL-17 has been recently identified as a key cytokine involved in numerous autoimmune processes. However, its role in liver autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is characterized histologically by autoreactive CD4 and CD8 T cells surrounding damaged bile ducts. CD4+ T cells are a major source of IL-17, which compose a distinct T helper subset (Th17). Thus we set out determine the role of IL-17 in both human and a murine model of PBC in a liver-targeted manner. Our data demonstrate an increase in the frequency of IL-17+ lymphocytic infiltration in liver tissues from PBC patients and those with other liver dysfunctions as compared to healthy livers. IL-2 receptor α knockout mice, a recently identified murine model of human PBC, also demonstrate marked aggregations of IL-17 positive cells within portal tracts and increased frequencies of Th17 cells in the liver compared to the periphery. Interestingly, CD4+ T cells from livers of normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from spleens, indicating a preferential induction of Th17 cells in liver tissues. Importantly, C57BL/6J cocultures of splenic CD4+ T cells and liver non-parenchymal cells increased IL-17 production approximately 10 fold compared to T cells alone, suggesting a role of the liver microenvironment in Th17 induction in cases of liver autoimmunity and other liver inflammatory diseases.
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DOI：
10.1006/clin.1996.0129
发表时间：
1996-09-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
Krams, SM;Cao, S;Martinez, OM
通讯作者：
Martinez, OM
影响因子：
4.4
作者：
Rutitzky, Laura I.;Bazzone, Lindsey;Stadecker, Miguel J.
通讯作者：
Stadecker, Miguel J.
影响因子：
30.5
作者：
Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
通讯作者：
Pulendran, Bali
影响因子：
9.1
作者：
Nagano, T;Yamamoto, K;Tsuji, T
通讯作者：
Tsuji, T
DOI：
10.1196/annals.1309.031
发表时间：
2004-01-01
期刊：
ORAL TOLERANCE: NEW INSIGHTS AND PROSPECTS FOR CLINICAL APPLICATION
影响因子：
--
作者：
Battaglia, M;Gianfrani, C;Roncarolo, MG
通讯作者：
Roncarolo, MG