Arachidonic acid activates NLRP3 inflammasome in MDSCs via FATP2 to promote post-transplant tumour recurrence in steatotic liver grafts

• DOI: 10.1016/j.jhepr.2023.100895
• Publication Date: 2023-08-22T06:42:39Z
• Authors: Hui Liu; Wai Ho Oscar Yeung; Li Pang; Jiang Liu; Xiao Bing Liu; Kevin Tak Pan Ng; Qingmei Zhang; Wen Qi Qiu; Yueqin Zhu; Tao Ding; Zhe Wang; Ji Ye Zhu; Chung Mau Lo; Kwan Man
• Keywords: Myeloid-derived Suppressor Cell; Fatty Acid Metabolism

The steatotic grafts have been applied in liver transplantation frequently owing to the high incidence of non-alcoholic fatty disease. However, livers are vulnerable graft injury. Myeloid-derived suppressor cell (MDSC) recruitment during injury promotes tumour recurrence. Lipid metabolism exerts immunological influence on MDSCs progression. Here, we aimed explore role and mechanism inflammasome activation induced by lipid subsequent effects recurrence.MDSC populations nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) levels were investigated a clinical cohort rat model. NLRP3 specific acids was explored mouse hepatic ischaemia/reperfusion (IRI) with recurrence model vitro studies.MDSC increased higher recurrent rate patients using grafts. upregulated accumulation post IRI. Mechanistically, arachidonic acid discovered activate through transport protein 2 (FATP2), which identified screening uptake receptors. mitochondrial dysfunction enhanced reactive oxygen species bridged MDSCs, subsequently stimulated CD4+ T cells producing more IL-17 Blockade FATP2 inhibited production cells, IRI.During injury, activated FATP2, promote transplantation.The disease resulted frequent application donors transplantation. Our data showed that who underwent experienced We found led secretion promoted aberrant acute-phase