IMMUNOPATHOGENESIS OF ARTHRITIS IN MRL MICE

MRL 小鼠关节炎的免疫发病机制

• 批准号: 3810826
• 负责人: DAVID S. PISETSKY
• 金额: --
• 依托单位: DUKE UNIVERSITY
• 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/3810826
• 关键词: T lymphocyte; animal population genetics; autoimmune disorder; autoradiography; cell population study; cellular pathology; collagen disorder; cytokine; gene expression; gene interaction; genetic manipulation; genetic models; genetic regulation; genetic strain; histochemistry /cytochemistry; immunochemistry; immunomodulators; immunopathology; in situ hybridization; inflammation; joint disorder; laboratory mouse; lymphokines; messenger RNA; molecular pathology; monoclonal antibody; monokines; nucleic acid hybridization; nucleic acid probes; oligonucleotides; rheumatoid arthritis; rheumatoid factor; serology /serodiagnosis; severe combined immunodeficiency; surface antigens; synovial membrane; synovitis

Autoimmune MRL-1pr mice develop an arthropathy with clinical and histological features in common with rheumatoid arthritis (RA). To elucidate the immunopathogenesis of this spontaneous disease model, it is proposed to identify effector mechanisms through genetic and cellular analysis. 1pr congenic mice and informative F1 and F2 generations will be studied to determine whether 1pr is itself sufficient for arthritis or requires interaction with other genes. To assess cellular mechanisms of disease, MRL- 1pr mice will be treated with various immunomodulatory agents such as monoclonal antibodies to L3T4 and Ia antigens. The nature of the cells infiltrating the synovium in both untreated and treated mice will then be investigated using immunohistologic techniques to characterize cell surface markers. The production of cytokines will also be evaluated in the synovium by in situ hybridization using probes for various mediators that have been postulated to promote joint changes. Finally, findings with MRL- 1pr mice will be compared with those observed in mice with collagen-induced arthritis, a model in which the role of T-cells is more defined. Together, these studies should help elucidate important facets of MRL-1pr arthritis and help assess its relationship to processes occurring in the RA joint.

自身免疫 MRL-1pr 小鼠出现临床关节病 和与类风湿性关节炎共同的组织学特征 （RA）。 为了阐明这种自发的免疫发病机制 疾病模型，建议确定效应机制 通过遗传和细胞分析。 1pr同类小鼠和 将研究信息丰富的 F1 和 F2 代以确定 1pr 本身是否足以治疗关节炎或需要相互作用 与其他基因。 为了评估疾病的细胞机制，MRL- 1pr小鼠将接受各种免疫调节剂治疗 例如针对 L3T4 和 Ia 抗原的单克隆抗体。 这 未经治疗和未经治疗的细胞浸润滑膜的性质 然后将使用免疫组织学方法对接受治疗的小鼠进行研究 表征细胞表面标记的技术。 生产 滑膜中的细胞因子也将通过原位评估 使用针对各种介体的探针进行杂交 假设促进联合变革。 最后，MRL 的研究结果- 1pr 小鼠将与在 1pr 小鼠中观察到的小鼠进行比较 胶原诱导的关节炎，T 细胞在该模型中的作用 更明确。 总之，这些研究应该有助于阐明 MRL-1pr 关节炎的重要方面并帮助评估其 与 RA 关节中发生的过程的关系。