Role of Innate and Adaptive Immune Systems in Drug-Induced Liver Disease

先天性和适应性免疫系统在药物性肝病中的作用

• 批准号: 8175407
• 负责人: Lance R Pohl
• 金额: $ 29.61万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8175407
• 关键词: Acids; Adjuvant; Animal Model; Animals; Antibodies; Anticonvulsants; Antigen-Presenting Cells; Autoimmune Diseases; Categories; Cells; Chloride Ion; Chlorides; Clinical; Disulfiram; Drug toxicity; Endothelial Cells; Erythromycin; Ethanol; Female; Halothane; Hepatic; Hepatocyte; Human; Immune; Immune response; Immune system; Infiltration; Injury; Kupffer Cells; Liver; Mediating; Mus; Pharmaceutical Preparations; Predisposition; Process; Proteins; Reaction; Regulatory T-Lymphocyte; Reporting; Role; Serum; Sulfonamides; T-Cell Proliferation; T-Lymphocyte; Transforming Growth Factor beta; adduct; drug induced liver disease; immunopathology; prevent; troglitazone

In this report, we compared the adaptive immune responses following halothane treatment of normal female Balb/cJ mice to Balb/cJ mice depleted of regulatory T cells. Mice depleted of regulatory T cells had significantly higher serum levels of anti-TFA-protein antibodies and elevated T cell proliferation when treated in culture with TFA-protein adducts as compared to normal Balb/cJ mice. Moreover, there was a significant infiltration of TGF-beta-producing T regulatory cells into the liver of normal Balb/cJ mice following halothane treatment. These results suggest that T regulatory cells may have an important inhibitory effect on the adaptive immune system reaction against protein adducts of drugs released from damaged hepatocytes and immunopathology against the liver. Conclusion: These preliminary findings warrant further studies into the role of regulatory T cells in the mechanisms and susceptibility to DILD.

在本报告中，我们比较了正常雌性 Balb/cJ 小鼠与耗尽调节性 T 细胞的 Balb/cJ 小鼠在氟烷治疗后的适应性免疫反应。与正常 Balb/cJ 小鼠相比，用 TFA 蛋白加合物培养时，调节性 T 细胞耗尽的小鼠血清中抗 TFA 蛋白抗体水平显着升高，T 细胞增殖也升高。此外，在氟烷治疗后，正常 Balb/cJ 小鼠的肝脏中产生 TGF-β 的 T 调节细胞显着浸润。这些结果表明，调节性T细胞可能对受损肝细胞释放的药物蛋白加合物的适应性免疫系统反应和针对肝脏的免疫病理学具有重要的抑制作用。 结论：这些初步发现值得进一步研究调节性 T 细胞在 DILD 机制和易感性中的作用。