Type 3 innate lymphoid cell: a new player in liver fibrosis progression.
Type 3 innate lymphoid cell: a new player in liver fibrosis progression.
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DOI：
10.1042/cs20180482
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发表时间：
2018-12
期刊：
影响因子：
6
通讯作者：
Si-Qi Wang;Jing Li;Shengdi Wu;Li-Sha Cheng;Yue Shen;Wei Ma;Wei‐Min She;Chang-qing Yang;Ji‐yao Wang;Wei Jiang
中科院分区：
文献类型：
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作者：
Si-Qi Wang;Jing Li;Shengdi Wu;Li-Sha Cheng;Yue Shen;Wei Ma;Wei‐Min She;Chang-qing Yang;Ji‐yao Wang;Wei Jiang
3型先天性淋巴样细胞（ILC 3）最近已成为炎症和纤维化疾病的关键效应。本研究旨在确定ILC 3在肝纤维化中的作用。通过流式细胞术，我们记录了患者外周ILC 3（Lin-CD 127 + CD 117 + CD 294-淋巴细胞）的频率增加，特别是在B型肝炎病毒（HBV）相关慢性肝病的晚期，并证明了它们与疾病进展的相关性。通过与LX-2（人肝星状细胞（HSC）系）的共培养实验来确定ILC 3的体外纤维化作用。这些数据表明，致病性ILC 3可以通过产生白细胞介素（IL）-17 A和IL-22以非接触方式直接促进LX-2纤维形成。此外，它们通过产生IL-22来抑制其他免疫细胞产生干扰素（IFN）-γ（一种众所周知的抗纤维化细胞因子），从而具有间接的纤维化作用。在四氯化碳（CCl 4）诱导的野生型小鼠肝纤维化模型中，我们还记录了肝脏和脾脏标本中非自然杀伤（NK）ILC（Lin-CD 127+淋巴细胞）和ILC 3（Lin-CD 127 +RORγt+淋巴细胞）的频率显著增加。此外，来自纤维化小鼠的ILC 3比来自正常和纤维化较少的小鼠的ILC 3含有更多的IL-17 A + ILC 3和IL-22+ ILC 3亚群。使用具有ILC耗竭的RAG-1-/-小鼠和来自野生型小鼠的ILC 3的进一步过继转移进一步确定ILC 3在肝纤维化中的体内作用。肝脏标本的免疫组织化学染色显示了CCl 4诱导的小鼠肝纤维化模型中ILC耗竭的有益作用和ILC 3转移的有害作用。总的来说，ILC 3在肝纤维化进展中起促纤维化作用。
Type 3 innate lymphoid cell (ILC3) has recently emerged as a crucial effector in inflammatory and fibrotic diseases. The present study was designed to determine the roles of ILC3 in liver fibrosis. By flow cytometry, we documented increased frequencies of peripheral ILC3 (Lin-CD127+CD117+CD294- lymphocytes) in patients, especially at the advanced stage of hepatitis B virus (HBV)-related chronic liver diseases, and demonstrated their correlations with disease progression. The in vitro fibrogenic effects by ILC3 were determined by co-culture experiments with LX-2 (a human hepatic stellate cell (HSC) line). The data indicate that pathogenic ILC3 can directly promote LX-2 fibrogenesis in non-contact manners by producing interleukin (IL)-17A and IL-22. Additionally, they had indirect fibrogenic effects by producing IL-22 to suppress interferon (IFN)-γ (a well-known anti-fibrotic cytokine) production by other immune cells. In carbon tetrachloride (CCl4)-induced wild-type mouse liver fibrosis models, we also documented significantly increased frequencies of both non-natural killer (NK) ILC (Lin-CD127+ lymphocytes) and ILC3 (Lin-CD127+RORγt+ lymphocytes) in liver and spleen specimens. Furthermore, the ILC3 from fibrotic mice contained more IL-17A+ILC3 and IL-22+ILC3 subsets than those from normal and less-fibrotic mice. The in vivo effects of ILC3 in liver fibrogenesis were further determined using RAG-1-/- mice with ILC depletion and further adoptive transfer of ILC3 from wild-type mice. The immunohistochemical staining of liver specimens showed the beneficial effects by ILC depletion and the detrimental effects by ILC3 transfer in CCl4-induced mouse liver fibrosis models. Collectively, ILC3 plays a pro-fibrotic role in liver fibrosis progression.