Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Life Sci. 2019 Sep 1;232:116653. doi: 10.1016/j.lfs.2019.116653. Epub 2019 Jul 11.
Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the gene encoding the huntingtin protein (HTT). This expansion leads to the formation of mutant huntingtin protein (mHTT) that is expressed in many body tissue cells. The mHTT interacts with several molecular pathways within different cell types, affecting the regulation of the immune system cells. It is still very limited the understanding of the immune changes in peripheral tissues in HD. Herein, we investigated the levels of inflammatory and regulatory cytokines in peripheral organs (i.e. kidney, heart, liver and spleen) of the 12-month-old BACHD model of HD. This robust murine model closely resembles the human disease. We found significant changes in cytokine levels in all organs analyzed. Increased levels of IL-6 were found in the kidney, while levels of IL-6 and IL-12p70 were increased in the heart of BACHD mice in comparison with wild-type (WT) animals. In the liver, we observed enhanced IL-12p70 and TNF-α levels. In the spleen, there was an increase in the levels of IL-4 and a decrease in the levels of IL-5 and IL-6 in BACHD compared to WT. Our findings provide the first evidence that the BACHD model also exhibits immune changes in peripheral organs, opening an avenue for the investigation of the potential role played by peripheral inflammatory response in HD. Further studies are needed to systematically address the mechanisms and pathways underlying immune signaling in peripheral organs in HD.
亨廷顿病（HD）是一种神经退行性疾病，由编码亨廷顿蛋白（HTT）的基因中的 CAG 重复扩展引起。这种扩展导致突变的亨廷顿蛋白（mHTT）的形成，该蛋白在许多身体组织细胞中表达。mHTT 与不同细胞类型中的几种分子途径相互作用，影响免疫系统细胞的调节。对于 HD 外周组织中的免疫变化，我们的理解仍然非常有限。在此，我们研究了 12 个月大的 BACHD HD 模型外周器官（即肾脏、心脏、肝脏和脾脏）中炎症和调节细胞因子的水平。这种强大的鼠模型非常类似于人类疾病。我们发现所有分析的器官中的细胞因子水平都发生了显著变化。在肾脏中发现 IL-6 水平升高，而与野生型（WT）动物相比，BACHD 小鼠心脏中的 IL-6 和 IL-12p70 水平升高。在肝脏中，我们观察到增强的 IL-12p70 和 TNF-α 水平。在脾脏中，与 WT 相比，BACHD 中的 IL-4 水平增加，IL-5 和 IL-6 水平降低。我们的研究结果首次提供了证据，表明 BACHD 模型在外周器官中也表现出免疫变化，为研究外周炎症反应在 HD 中的潜在作用开辟了途径。需要进一步的研究来系统地解决 HD 外周器官中免疫信号转导的机制和途径。
