title: Regulatory T cells ameliorate acetaminophen-induced immune-mediated liver injury.
abstract: The contribution of innate immune cells to acetaminophen (APAP)-induced liver injury has been extensively investigated. However, the roles of T cell populations among adaptive immune cells in APAP-induced liver injury remain to be elucidated. Herein, we found that distinct CD4(+) T cell subsets but not CD8(+) T cells modulated APAP-induced liver injury in mice. After APAP challenge, more CD62L(low)CD44(hi)CD4(+) T cells appeared in the liver, accompanied by increased IFN-γ. The removal of CD4(+) T cells by either antibody depletion or genetic deficiency markedly compromised pro-inflammatory cytokine levels and ameliorated liver injury. Meanwhile, we also found that the frequency and absolute number of Treg cells also increased. Treg cell depletion increased hepatic CD62L(low)CD44(hi)CD4(+) T cells, augmented pro-inflammatory cytokines, and exacerbated liver injury, while adoptive transfer of Treg cells ameliorated APAP-induced liver injury. Furthermore, the recruitment of Treg cells into the liver through specific expression of CXCL10 in the liver could ameliorate APAP-induced liver injury. Our investigation suggests that Th1 and Treg subsets are involved in regulating APAP-induced liver injury. Thus, modulating the Th1/Treg balance may be an effective strategy to prevent and/or treat APAP-induced liver injury.
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China.
authors: Xuefu
authors: X
authors: Wang
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors: Rui
authors: R
authors: Sun
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China.
authors: Yongyan
authors: Y
authors: Chen
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors: Zhe-Xiong
authors: ZX
authors: Lian
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors: Haiming
authors: H
authors: Wei
authors: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. Electronic address: tzg@ustc.edu.cn.
authors: Zhigang
authors: Z
authors: Tian
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D018398:Homeodomain Proteins / Q000235:genetics; D008099:Liver / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; C064658:RAG-1 protein; D000082:Acetaminophen
keywords: Acetaminophen; Adaptive immune cells; CXCL10; Liver injury; Regulatory T cells