Intrahepatic infiltration of activated CD8+ T cells and mononuclear phagocyte is associated with idiosyncratic drug-induced liver injury

Frontiers in Immunology

Immunology

Eun Sun Jung¹  Jae Jun Lee²  Pu Reun Rho²  Sung Woo Cho²  Min-Woo Kang²  Ahlim Lee³  Hyun Yang³  Si Hyun Bae³  Jong Young Choi⁴  Pil Soo Sung⁴  Jeong Won Jang⁴  Ji Won Han⁴ 

[1] Department of Hospital Pathology, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea;The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;Division of Hepatology, Department of Internal medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea;The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;Division of Hepatology, Department of Internal medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea;

关键词: drug-induced liver injury;    T cell;    mononuclear phagocyte;    flow cytometry;    steroid;   

DOI  :  10.3389/fimmu.2023.1138112

 received in 2023-01-05, accepted in 2023-02-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundIdiosyncratic drug-induced liver injury (DILI) is caused by the interplay among drugs, their metabolites, and the host immune response. The characterization of infiltrated immune cells in the liver may improve the understanding of the pathogenesis of idiosyncratic DILI. This study investigated the phenotypes and clinical implications of liver-infiltrating immune cells in idiosyncratic DILI.MethodsFrom January 2017 to June 2021, 53 patients with idiosyncratic DILI who underwent liver biopsy were prospectively enrolled in this study. Immunohistochemical staining and flow cytometry analyses were performed on the biopsy specimens. Serum levels of CXC chemokine ligand 10 (CXCL10) and soluble CD163 were measured. A multivariate cox proportional hazards model was used to evaluate predictors of DILI resolution within 30 days.ResultsThe numbers of intrahepatic T cells and mononuclear phagocytes were positively correlated with serum levels of total bilirubin, alanine aminotransferase (ALT), and the model of end-stage liver disease score. The frequency of activated CD8+ T cells among liver-infiltrating CD8+ T cells in DILI livers was higher than that in healthy livers. Notably, the percentages of activated intrahepatic CD8+ T cells and mononuclear phagocytes in DILI livers showed a positive correlation with ALT. Additionally, serum CXCL10 level was positively correlated with intrahepatic T cell infiltration and ALT, and soluble CD163 level was positively correlated with intrahepatic mononuclear phagocyte infiltration and ALT. Thirty-six patients (70.6%) were treated with steroids. In multivariate analysis, total bilirubin and steroid use independently influenced DILI resolution within 30 days.ConclusionsActivated CD8+ T cells and mononuclear phagocyte are associated with liver injury caused by drugs. Therefore, we suggest that steroids are a potential treatment option for idiosyncratic DILI.

【 授权许可】

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Copyright © 2023 Yang, Han, Lee, Lee, Cho, Rho, Kang, Jang, Jung, Choi, Sung and Bae