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: 8344879
• 负责人: Lance R Pohl
• 金额: $ 49.54万
• 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/8344879
• 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; Infection; Injury; Kupffer Cells; Liver; Mediating; Mus; Myelogenous; Pharmaceutical Preparations; Predisposition; Process; Proteins; Reaction; Regulatory T-Lymphocyte; Reporting; Role; Sulfonamides; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; adduct; drug induced liver disease; immunopathology; in vivo; prevent; troglitazone; tumor

Last year we found that regulatory T cells infiltrated into the liver of female Balb/cJ mice following halothane treatment and inhibited both humoral and cellular immune reactions against trifluoroacetylated proteins formed in vivo following halothane treatment. This year we report that newly discovered myeloid-derived suppressor cells also infiltrated into the liver of female Balb/cJ mice following halothane treatment. These cells have be shown recently to inhibit effector T cell activity in tumors, infections, and in autoimmune diseases. Conclusion: These findings suggest that both regulatory T cells and myeloid-derived suppressor cells might have a role in preventing drug-protein adducts from causing liver injury mediated by the adaptive immune system and that deficiencies in the activities of these regulatory cells might be susceptibility factors in DILD.

去年，我们发现在氟烷治疗后，调节性 T 细胞渗入雌性 Balb/cJ 小鼠的肝脏，并抑制针对氟烷治疗后体内形成的三氟乙酰化蛋白的体液和细胞免疫反应。 今年，我们报告新发现的骨髓源性抑制细胞在氟烷治疗后也渗入雌性 Balb/cJ 小鼠的肝脏中。最近显示这些细胞可以抑制肿瘤、感染和自身免疫性疾病中的效应 T 细胞活性。 结论：这些研究结果表明，调节性T细胞和髓源性抑制细胞可能在防止药物-蛋白加合物引起适应性免疫系统介导的肝损伤方面发挥作用，并且这些调节细胞活性的缺陷可能是DILD的易感因素。