Inhibition of crosstalk between iNKT cells and macrophages mitigates ischemia-reperfusion injury in steatotic livers

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Yu Kuroda , Yoshiya Ito , Nobuyuki Nishizawa , Mina Tanabe , Atsushi Yamashita , Kanako Hosono , Mariko Kamata , Masashi Satoh , Yusuke Kumamoto , Naoki Hiki , Hideki Amano
{"title":"Inhibition of crosstalk between iNKT cells and macrophages mitigates ischemia-reperfusion injury in steatotic livers","authors":"Yu Kuroda ,&nbsp;Yoshiya Ito ,&nbsp;Nobuyuki Nishizawa ,&nbsp;Mina Tanabe ,&nbsp;Atsushi Yamashita ,&nbsp;Kanako Hosono ,&nbsp;Mariko Kamata ,&nbsp;Masashi Satoh ,&nbsp;Yusuke Kumamoto ,&nbsp;Naoki Hiki ,&nbsp;Hideki Amano","doi":"10.1016/j.yexcr.2025.114728","DOIUrl":null,"url":null,"abstract":"<div><div>Liver ischemia-reperfusion (IR) injury is a substantial form of damage that occurs during liver transplantation and resection surgeries. Steatotic livers are particularly susceptible to IR injury, but few strategies to effectively alleviate this issue in steatotic livers exist. Invariant natural killer T (iNKT) cells regulate IR injury in healthy livers as well as liver repair by interacting with macrophages. In this study, we explored the role of iNKT cell-macrophage crosstalk in IR injury in steatotic livers. High-fat diet (HFD)-fed macrophage-specific CD1d conditional knockout (<em>Cd1d</em><sup><em>△mac</em></sup>) and Cd1d<sup>flox</sup> control (Cont) mice were subjected to liver IR. HFD-fed <em>CD1d</em><sup><em>△mac</em></sup> mice showed mitigation of IR-induced liver damages with reduction of hepatic necrosis and inflammation along with promotion of liver repair. Flow cytometric analysis revealed that HFD-fed <em>Cd1d</em><sup><em>△mac</em></sup> mice showed increased hepatic reparative macrophages and interleukin (IL)-13-positive iNKT cells but decreased pro-inflammatory macrophages with IL-1β. IL-13 administration to HFD-fed Cont mice attenuated IR injury and accelerated liver recovery, which was associated with accumulation of hepatic macrophages skewed to a reparative phenotype. IL-13 promoted reparative macrophage polarization in bone marrow (BM)-derived <em>Cd1d</em>-deficient macrophages in vitro. Blockade of IL-13 in HFD-fed <em>Cd1d</em><sup><em>△mac</em></sup> mice aggravated IR injury. Overall, inhibiting iNKT cell-macrophage crosstalk attenuates steatotic liver IR injury and facilitates liver repair via IL-13-mediated reparative macrophage polarization. These findings provide new insights into therapeutic strategies to regulate the vulnerability of the steatotic liver to IR injury.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114728"},"PeriodicalIF":3.5000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental cell research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014482725003283","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Liver ischemia-reperfusion (IR) injury is a substantial form of damage that occurs during liver transplantation and resection surgeries. Steatotic livers are particularly susceptible to IR injury, but few strategies to effectively alleviate this issue in steatotic livers exist. Invariant natural killer T (iNKT) cells regulate IR injury in healthy livers as well as liver repair by interacting with macrophages. In this study, we explored the role of iNKT cell-macrophage crosstalk in IR injury in steatotic livers. High-fat diet (HFD)-fed macrophage-specific CD1d conditional knockout (Cd1d△mac) and Cd1dflox control (Cont) mice were subjected to liver IR. HFD-fed CD1d△mac mice showed mitigation of IR-induced liver damages with reduction of hepatic necrosis and inflammation along with promotion of liver repair. Flow cytometric analysis revealed that HFD-fed Cd1d△mac mice showed increased hepatic reparative macrophages and interleukin (IL)-13-positive iNKT cells but decreased pro-inflammatory macrophages with IL-1β. IL-13 administration to HFD-fed Cont mice attenuated IR injury and accelerated liver recovery, which was associated with accumulation of hepatic macrophages skewed to a reparative phenotype. IL-13 promoted reparative macrophage polarization in bone marrow (BM)-derived Cd1d-deficient macrophages in vitro. Blockade of IL-13 in HFD-fed Cd1d△mac mice aggravated IR injury. Overall, inhibiting iNKT cell-macrophage crosstalk attenuates steatotic liver IR injury and facilitates liver repair via IL-13-mediated reparative macrophage polarization. These findings provide new insights into therapeutic strategies to regulate the vulnerability of the steatotic liver to IR injury.
抑制iNKT细胞和巨噬细胞之间的串扰可减轻脂肪变性肝缺血再灌注损伤
肝缺血再灌注(IR)损伤是肝移植和肝切除手术中发生的一种重要损伤形式。脂肪变性肝脏特别容易受到IR损伤,但很少有策略可以有效地缓解脂肪变性肝脏的这一问题。不变性自然杀伤T (iNKT)细胞通过与巨噬细胞相互作用调节健康肝脏的IR损伤和肝脏修复。在这项研究中,我们探讨了iNKT细胞-巨噬细胞串扰在脂肪变性肝脏IR损伤中的作用。高脂饮食(HFD)喂养巨噬细胞特异性CD1d条件敲除(CD1d△mac)和Cd1dflox对照(Cont)小鼠进行肝脏IR。hfd喂养的CD1d△mac小鼠表现出减轻ir诱导的肝脏损伤,减少肝坏死和炎症,促进肝脏修复。流式细胞分析显示,hfd喂养的Cd1d△mac小鼠肝脏修复性巨噬细胞和白细胞介素(IL)-13阳性iNKT细胞增加,促炎巨噬细胞IL-1β减少。给hfd喂养的小鼠注射IL-13可减轻IR损伤,加速肝脏恢复,这与肝巨噬细胞偏向修复表型的积累有关。IL-13在体外促进骨髓(BM)来源的cd1缺陷巨噬细胞的修复性巨噬细胞极化。阻断hfd喂养的Cd1d△mac小鼠IL-13可加重IR损伤。总体而言,抑制iNKT细胞-巨噬细胞串扰可减轻脂肪变性肝IR损伤,并通过il -13介导的修复性巨噬细胞极化促进肝脏修复。这些发现为调节脂肪变性肝对IR损伤的易感性的治疗策略提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信