Type 1 Innate Lymphoid Cells Are Proinflammatory Effector Cells in Ischemia-Reperfusion Injury of Steatotic Livers.
Type 1 Innate Lymphoid Cells Are Proinflammatory Effector Cells in Ischemia-Reperfusion Injury of Steatotic Livers.
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DOI：
10.3389/fimmu.2022.899525
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发表时间：
2022
影响因子：
7.3
通讯作者：
Kroemer, Alexander
中科院分区：
文献类型：
--
作者：
Kang, Jiman;Liggett, Jedson R.;Patil, Digvijay;Ranjit, Suman;Loh, Katrina;Duttargi, Anju;Cui, Yuki;Oza, Kesha;Frank, Brett S.;Kwon, DongHyang;Kallakury, Bhaskar;Robson, Simon C.;Fishbein, Thomas M.;Cui, Wanxing;Khan, Khalid;Kroemer, Alexander
关键词：
先天性淋巴样细胞（inate lymphoid cells，ILC）是近年来发现的一类淋巴样细胞，通过产生关键的细胞因子，在维持组织内环境稳定中发挥重要作用。第1组ILC，包括传统的自然杀伤细胞（cNK）和1型ILC（ILC 1），已涉及调节免疫介导的炎症性疾病。然而，ILC 1在非酒精性脂肪性肝病（NAFLD）和缺血再灌注损伤（IRI）中的作用尚不清楚。在这里，我们研究了ILC 1和cNK细胞在高脂饮食（HFD）小鼠模型中的作用。我们证明，与非脂肪变性肝脏相比，脂肪变性肝脏导致更严重的IRI。我们进一步得出HFD-IRI小鼠显示ILC 1群体显著增加，而cNK群体不变。由于ILC 1和cNK是IFN-γ和TNF-α的主要来源，我们测量了正常饮食（ND）-IRI和HFD-IRI条件下的离体细胞因子表达水平。我们发现，与ND-IRI相比，HFD-IRI小鼠中的ILC 1产生显著更多的IFN-γ和TNF-α。为了进一步评估ILC 1是否是脂肪肝肝IRI中的关键促炎效应细胞，我们研究了具有cNK细胞的Rag 1 −/−小鼠和大量ILC 1与新产生的Rag 1 −/− Tbx 21 −/−双敲除（Rag 1-Tbet DKO）小鼠，后者缺乏1型ILC，在HFD IRI条件下。重要的是，与Rag 1 −/−小鼠相比，HFD Rag 1-Tbet DKO小鼠在IRI时显示出显著的肝损伤保护作用，表明表达T-bet的ILC 1至少部分地在脂肪变性条件下的肝IRI中发挥促炎效应细胞的作用。
Innate lymphoid cells (ILCs), the most recently described family of lymphoid cells, play fundamental roles in tissue homeostasis through the production of key cytokine. Group 1 ILCs, comprised of conventional natural killer cells (cNKs) and type 1 ILCs (ILC1s), have been implicated in regulating immune-mediated inflammatory diseases. However, the role of ILC1s in nonalcoholic fatty liver disease (NAFLD) and ischemia-reperfusion injury (IRI) is unclear. Here, we investigated the role of ILC1 and cNK cells in a high-fat diet (HFD) murine model of partial warm IRI. We demonstrated that hepatic steatosis results in more severe IRI compared to non-steatotic livers. We further elicited that HFD-IRI mice show a significant increase in the ILC1 population, whereas the cNK population was unchanged. Since ILC1 and cNK are major sources of IFN-γ and TNF-α, we measured the level of ex vivo cytokine expression in normal diet (ND)-IRI and HFD-IRI conditions. We found that ILC1s in HFD-IRI mice produce significantly more IFN-γ and TNF-α when compared to ND-IRI. To further assess whether ILC1s are key proinflammatory effector cells in hepatic IRI of fatty livers, we studied both Rag1 −/− mice, which possess cNK cells, and a substantial population of ILC1s versus the newly generated Rag1 −/− Tbx21 −/− double knockout (Rag1-Tbet DKO) mice, which lack type 1 ILCs, under HFD IRI conditions. Importantly, HFD Rag1-Tbet DKO mice showed significant protection from hepatic injury upon IRI when compared to Rag1 −/− mice, suggesting that T-bet-expressing ILC1s play a role, at least in part, as proinflammatory effector cells in hepatic IRI under steatotic conditions.
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影响因子：
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Kaldas, Fady M.
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