Peiying Wang, Yiran Zheng, Jiaman Sun, Yumo Zhang, Wing Keung Chan, Yan Lu, Xiaohong Li, Zhouxin Yang, Youwei Wang
{"title":"Sepsis induced dysfunction of liver type 1 innate lymphoid cells.","authors":"Peiying Wang, Yiran Zheng, Jiaman Sun, Yumo Zhang, Wing Keung Chan, Yan Lu, Xiaohong Li, Zhouxin Yang, Youwei Wang","doi":"10.1186/s12865-024-00648-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening condition triggered by uncontrolled immune responses to infection, leading to widespread inflammation, tissue damage, organ dysfunction, and potentially death. The liver plays a crucial role in the immune response during sepsis, serving as a major site for immune cell activation and cytokine production. Liver type 1 innate lymphoid cells (ILCs) consist of NK cells and ILC1s. They maintain the local immune microenvironment by directly eliminating target cells and secreting cytokines. However, the specific roles and pathological changes of liver-resident NK cells and ILC1s during sepsis remain poorly understood.</p><p><strong>Results: </strong>This study aims to investigate the pathological changes of NK cells and ILC1s, which might contribute the dysfunction of liver. Sepsis mouse model was established by cecal ligation and puncture (CLP). Mouse immune cells from liver were isolated, and the surface makers, gene expression profiles, cytokine response and secretion, and mitochondrial function of NK (Natural Killer) cells and ILC1s (Innate Lymphoid Cell 1) were analyzed. A significant decrease in the number of mature NK cells was observed in the liver after CLP. Furthermore, the secretion of interferon-gamma (IFN-γ) was found to be reduced in spleen and liver NK cells when stimulated by IL-18. Mitochondrial activities in both liver NK cells and ILC1 were found to be increased during sepsis, suggesting an enhanced metabolic response in these cells to combat the infection. However, despite this heightened activity, liver NK cells exhibited a decreased level of cytotoxicity, which might impact their ability to target infected cells effectively. RNA sequencing supported and provided the potential mechanisms for the proinflammatory effects and exhaustion like phenotypes of liver NK cells.</p><p><strong>Conclusions: </strong>Sepsis induces dysfunction and exhaustion-like phenotypes in liver NK cells and ILC1, which might further impair other immune cells and represent a potential therapeutic target for sepsis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363412/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12865-024-00648-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Sepsis is a life-threatening condition triggered by uncontrolled immune responses to infection, leading to widespread inflammation, tissue damage, organ dysfunction, and potentially death. The liver plays a crucial role in the immune response during sepsis, serving as a major site for immune cell activation and cytokine production. Liver type 1 innate lymphoid cells (ILCs) consist of NK cells and ILC1s. They maintain the local immune microenvironment by directly eliminating target cells and secreting cytokines. However, the specific roles and pathological changes of liver-resident NK cells and ILC1s during sepsis remain poorly understood.
Results: This study aims to investigate the pathological changes of NK cells and ILC1s, which might contribute the dysfunction of liver. Sepsis mouse model was established by cecal ligation and puncture (CLP). Mouse immune cells from liver were isolated, and the surface makers, gene expression profiles, cytokine response and secretion, and mitochondrial function of NK (Natural Killer) cells and ILC1s (Innate Lymphoid Cell 1) were analyzed. A significant decrease in the number of mature NK cells was observed in the liver after CLP. Furthermore, the secretion of interferon-gamma (IFN-γ) was found to be reduced in spleen and liver NK cells when stimulated by IL-18. Mitochondrial activities in both liver NK cells and ILC1 were found to be increased during sepsis, suggesting an enhanced metabolic response in these cells to combat the infection. However, despite this heightened activity, liver NK cells exhibited a decreased level of cytotoxicity, which might impact their ability to target infected cells effectively. RNA sequencing supported and provided the potential mechanisms for the proinflammatory effects and exhaustion like phenotypes of liver NK cells.
Conclusions: Sepsis induces dysfunction and exhaustion-like phenotypes in liver NK cells and ILC1, which might further impair other immune cells and represent a potential therapeutic target for sepsis.
背景:败血症是一种危及生命的疾病,由感染后失控的免疫反应引发,导致广泛的炎症、组织损伤、器官功能障碍,甚至可能导致死亡。肝脏在败血症期间的免疫反应中起着至关重要的作用,是免疫细胞活化和细胞因子产生的主要场所。肝脏 1 型先天性淋巴细胞(ILCs)由 NK 细胞和 ILC1s 组成。它们通过直接消灭靶细胞和分泌细胞因子来维持局部免疫微环境。然而,人们对肝脏驻留的 NK 细胞和 ILC1s 在败血症期间的具体作用和病理变化仍知之甚少:本研究旨在探讨可能导致肝脏功能障碍的 NK 细胞和 ILC1s 的病理变化。通过盲肠结扎建立败血症小鼠模型。从肝脏中分离出小鼠免疫细胞,分析了NK(自然杀伤细胞)和ILC1s(先天淋巴细胞1)的表面形态、基因表达谱、细胞因子反应和分泌以及线粒体功能。观察发现,CLP 后肝脏中成熟 NK 细胞的数量明显减少。此外,在 IL-18 的刺激下,发现脾脏和肝脏 NK 细胞分泌的干扰素-γ(IFN-γ)减少。在败血症期间,肝脏 NK 细胞和 ILC1 的线粒体活性都有所增加,这表明这些细胞的新陈代谢反应增强,以对抗感染。然而,尽管肝脏NK细胞的活性增强了,但它们的细胞毒性却降低了,这可能会影响它们有效靶向受感染细胞的能力。RNA测序支持并提供了肝脏NK细胞促炎效应和衰竭表型的潜在机制:脓毒症会诱导肝脏NK细胞和ILC1出现功能障碍和衰竭样表型,这可能会进一步损害其他免疫细胞,并成为脓毒症的潜在治疗靶点。
期刊介绍:
BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.