Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.

Autor: Tasnim F; Innovations in Food & Chemical Safety Programme, ASTAR, Singapore, Singapore.; Institute of Bioengineering and Nanotechnology, The Nanos, Singapore, Singapore., Huang X; Innovations in Food & Chemical Safety Programme, ASTAR, Singapore, Singapore.; Institute of Bioengineering and Nanotechnology, The Nanos, Singapore, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Lee CZW; Innovations in Food & Chemical Safety Programme, ASTAR, Singapore, Singapore.; Singapore Immunology Network, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Ginhoux F; Innovations in Food & Chemical Safety Programme, ASTAR, Singapore, Singapore.; Singapore Immunology Network, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Yu H; Innovations in Food & Chemical Safety Programme, ASTAR, Singapore, Singapore.; Institute of Bioengineering and Nanotechnology, The Nanos, Singapore, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore, Singapore.; T-Labs, Mechanobiology Institute, Singapore, Singapore.; Critical Analytics for Manufacturing Personalised-Medicine Interdisciplinary Research Groups (CAMP-IRG), Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore, Singapore.
Jazyk: angličtina
Zdroj: Frontiers in toxicology [Front Toxicol] 2021 Apr 27; Vol. 3, pp. 605392. Date of Electronic Publication: 2021 Apr 27 (Print Publication: 2021).
DOI: 10.3389/ftox.2021.605392
Abstrakt: Hepatic inflammation is a key feature of a variety of liver diseases including drug-induced liver injury (DILI), orchestrated by the innate immune response (Kupffer cells, monocytes, neutrophils, dendritic cells) and the adaptive immune system (T cells and natural killer T cells). In contrast to acute DILI, prediction of immune-mediated DILI (im-DILI) has been more challenging due to complex disease pathogenesis, lack of reliable models and limited knowledge of underlying mechanisms. This review summarizes in vivo and in vitro systems that have been used to model im-DILI. In particular, the review focuses on state-of-the-art in vitro human-based multicellular models which have been developed to supplement the use of in vivo models due to interspecies variation and increasing ethical concerns regarding animal use. Advantages of the co-cultures in maintaining hepatocyte functions and importantly, introducing heterotypic cell-cell interactions to mimic inflammatory hepatic microenvironment are discussed. Challenges regarding cell source and incorporation of different cells with physical cell-cell contact are outlined and potential solutions are proposed. It is likely that better understanding of the interplay of immune cells in liver models will allow for the development of more accurate systems to better predict hepatotoxicity and stratification of drugs that can cause immune-mediated effects.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Tasnim, Huang, Lee, Ginhoux and Yu.)
Databáze: MEDLINE