Variations in T cell transcription factor gene structure and expression associated with the two disease forms of sheep paratuberculosis.
Variations in T cell transcription factor gene structure and expression associated with the two disease forms of sheep paratuberculosis.
复制标题
DOI：
10.1186/s13567-016-0368-3
复制
发表时间：
2016-08-17
影响因子：
4.4
通讯作者：
Hopkins J
中科院分区：
文献类型：
--
作者：
Nicol L;Wilkie H;Gossner A;Watkins C;Dalziel R;Hopkins J
绵羊临床副结核病有两种不同形式，与细菌定植水平有关。少杆菌病变主要由淋巴细胞和少量细菌组成，多杆菌病变的特点是巨噬细胞严重感染。细胞因子转录物分析表明，炎症性 Th1/Th17 T 细胞与少杆菌病理学的发展相关，而 Th2 细胞因子与多杆菌疾病相关。主调节 T 细胞转录因子 TBX21、GATA3、RORC2 和 RORA 对于这些 T 细胞亚群的发育至关重要。转录因子的序列变异也与人类分枝杆菌和胃肠道炎症性疾病的不同疾病形式有关。使用相对 RT-qPCR 来比较未感染对照和具有确定的少杆菌和多杆菌病理学的绵羊的回盲肠淋巴结中主调节因子的每个转录物变体的表达水平。多杆菌羊中低水平的 GATA3 未能证实多杆菌副结核病仅由 Th2 免疫反应引起。然而，高水平的 TBX21、RORC2 和 RORC2v1 凸显了 Th1 和 Th17 激活在少杆菌疾病中的作用。少杆菌组织中 RORAv1 水平升高表明 RORα 在绵羊 Th17 发育中发挥作用；而 RORAv4 水平升高表明该变异可能抑制 RORα 功能并抑制多杆菌羊中 Th17 的发育。本文的在线版本 (doi:10.1186/s13567-016-0368-3) 包含补充材料，可供授权用户使用。
Two different forms of clinical paratuberculosis in sheep are recognised, related to the level of bacterial colonization. Paucibacillary lesions are largely composed of lymphocytes with few bacteria, and multibacillary pathology is characterized by heavily-infected macrophages. Analysis of cytokine transcripts has shown that inflammatory Th1/Th17 T cells are associated with development of paucibacillary pathology and Th2 cytokines are correlated with multibacillary disease. The master regulator T cell transcription factors TBX21, GATA3, RORC2 and RORA are critical for the development of these T cell subsets. Sequence variations of the transcription factors have also been implicated in the distinct disease forms of human mycobacterial and gastrointestinal inflammatory diseases. Relative RT-qPCR was used to compare expression levels of each transcript variant of the master regulators in the ileo-caecal lymph nodes of uninfected controls and sheep with defined paucibacillary and multibacillary pathology. Low levels of GATA3 in multibacillary sheep failed to confirm that multibacillary paratuberculosis is caused simply by a Th2 immune response. However, high levels of TBX21, RORC2 and RORC2v1 highlights the role of Th1 and Th17 activation in paucibacillary disease. Increased RORAv1 levels in paucibacillary tissue suggests a role for RORα in Th17 development in sheep; while elevated levels of RORAv4 hints that this variant might inhibit RORα function and depress Th17 development in multibacillary sheep. The online version of this article (doi:10.1186/s13567-016-0368-3) contains supplementary material, which is available to authorized users.