2. Academic Validation
  3. Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury

Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury

  • Cell Rep Med. 2023 Jul 26;101132. doi: 10.1016/j.xcrm.2023.101132.
Na Yin 1,  Wenjun Zhang 1,  Xiao-Xin Sun 2,  Runxiu Wei 1,  Qiang Yang 1,  Fengming He 3,  Changrui Li 4,  Ling Guo 5,  Min Feng 6
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, China.
  • 2 Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
  • 3 School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen 361102, China.
  • 4 Guangzhou Zhixin High School, Zhixin South Road, Guangzhou 510080, China.
  • 5 School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, China; Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address: guoling@hainanu.edu.cn.
  • 6 School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, China. Electronic address: fengmin@mail.sysu.edu.cn.
PMID: 37541252 DOI: 10.1016/j.xcrm.2023.101132
Abstract

Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on Caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1β into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1β when liver reinjury occurs. In LIGHT of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.

Keywords

IL-1β; acute liver failure; artificial cells; itaconic acid; memory-like hepatic macrophages.

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