RORa enforces stability of the T-helper-17 cell effector program (RNA-Seq)

Chronic inflammation is responsible for a number of debilitating human diseases including inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis. The Th17 subset of T lymphocytes is an important player in the development of these pathogenic conditions. The transcription factor, RORgt was initially coined the master regulator of the Th17 program, but targeting RORgt therapeutically is dangerous owing to an enhanced risk of thymoma upon its inhibition. Another ROR family member, RORa, has also been implicated in Th17 function. Overall design: RNA-Seq: To investigate the molecular mechanism by which RORa regulates the Th17 program, TWT and TAKO Th17 cells were isolated from the DLN and SC of 3 separate cohorts of mixed chimeric mice based on their IL17AeGFP expression (see Figure 1G) at the peak of EAE disease, and their transcriptomes were sequenced (RNA-Seq)(Figures S3A-C).

慢性炎症是多种致残性人类疾病的重要诱因，涵盖炎症性肠病（inflammatory bowel disease）、多发性硬化症（multiple sclerosis）与类风湿关节炎（rheumatoid arthritis）。Th17型T淋巴细胞亚群是这类致病性疾病发生发展过程中的关键参与者。转录因子RORγt（RORgt）最初被定义为Th17细胞程序的核心调控因子，但治疗性靶向RORγt存在安全隐患：抑制该因子会提升胸腺瘤的发病风险。另一ROR家族成员RORα（RORa）同样被证实参与Th17细胞的功能调控。
实验总体设计：RNA测序（RNA-Seq）：为阐明RORα调控Th17细胞程序的分子机制，研究人员在实验性自身免疫性脑脊髓炎（EAE）疾病高峰期，依据IL17A-eGFP的表达特征（详见图1G），从3批混合嵌合小鼠的引流淋巴结（DLN）和脊髓（SC）中分离TWT与TAKO型Th17细胞，并对其转录组进行测序（RNA-Seq）（补充图S3A-C）。