Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China.
Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy.
Clin Rev Allergy Immunol. 2018 Apr;54(2):307-317. doi: 10.1007/s12016-017-8664-x.
Myeloid cells play a major role in the sensitization to liver injury, particularly in chronic inflammatory liver diseases with a biliary or hepatocellular origin, and the interplay between myeloid cells and the liver may explain the increased incidence of hepatic osteodystrophy. The myeloid cell-liver axis involves several mature myeloid cells as well as immature or progenitor cells with the complexity of the liver immune microenvironment aggravating the mist of cell differentiation. The unique positioning of the liver at the junction of the peripheral and portal circulation systems underlines the interaction of myeloid cells and hepatic cells and leads to immune tolerance breakdown. We herein discuss the scenarios of different chronic liver diseases closely modulated by myeloid cells and illustrate the numerous potential targets, the understanding of which will ultimately steer the development of solid immunotherapeutic regimens. Ultimately, we are convinced that an adequate modulation of the liver microenvironment to modify the functional and quantitative characteristics of myeloid cells will be a successful approach to treating chronic liver diseases of different etiologies.
髓系细胞在肝损伤的致敏中起主要作用,特别是在具有胆管或肝细胞来源的慢性炎症性肝病中,髓系细胞与肝脏的相互作用可能解释了肝性骨营养不良发生率的增加。髓系细胞-肝轴涉及几种成熟的髓系细胞以及不成熟或祖细胞,肝脏免疫微环境的复杂性加剧了细胞分化的混乱。肝脏在体循环和门静脉循环系统交界处的独特定位强调了髓系细胞与肝细胞的相互作用,并导致免疫耐受的破坏。我们在此讨论了由髓系细胞密切调节的不同慢性肝病的情况,并说明了许多潜在的靶点,对这些靶点的理解最终将指导有效的免疫治疗方案的发展。最终,我们相信适当调节肝脏微环境以改变髓系细胞的功能和数量特征将是治疗不同病因的慢性肝病的成功方法。