Department Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany.
Key Laboratory of Pathogenic Microbiology and Immunology, University of the Chinese Academy of Sciences, Beijing, 100080, China.
J Mol Med (Berl). 2018 Dec;96(12):1387-1394. doi: 10.1007/s00109-018-1706-x. Epub 2018 Oct 24.
Foxp3 regulatory T cells (Tregs) co-expressing the Th17-lineage specification factor RORγt represent a unique Treg subpopulation that has been reported to be induced upon response to gut microbiota within the intestinal immune system. Hence, RORγt Tregs are considered to solely consist of peripherally induced Foxp3 Tregs (pTregs), and the possibility that also thymus-derived Treg (tTregs) can upregulate RORγt expression and contribute to the pool of RORγt Tregs was largely ignored. Here, we expand our knowledge on the origin of RORγt Tregs by demonstrating that also tTregs can attain RORγt expression. In transgenic Foxp3 reporter mice, a substantial fraction of CNS1-independent Tregs, predominantly consisting of tTregs, was found to co-express RORγt. In addition, genuine tTregs isolated from thymi of Foxp3RAG reporter mice initiated RORγt expression both in vitro and in vivo, particularly under inflammatory conditions. In conclusion, our data demonstrate that tTregs can upregulate RORγt expression under inflammatory conditions and that hence RORγt Tregs can be regarded as a heterogeneous population consisting of both pTregs and tTregs. KEY MESSAGES: RORγt cannot be considered as a marker for pTregs. CNS1-independent tTregs within the colon display RORγt expression. RORγt can be induced in genuine tTregs, particularly under inflammatory conditions. RORγt Tregs are a heterogeneous population consisting of both pTregs and tTregs.
Foxp3 调节性 T 细胞 (Tregs) 共同表达 Th17 谱系特异性因子 RORγt，代表了一种独特的 Treg 亚群，据报道，这种 Treg 亚群在肠道免疫系统中对肠道微生物群的反应中被诱导产生。因此，RORγt Tregs 被认为仅由外周诱导的 Foxp3 Tregs（pTregs）组成，而胸腺衍生的 Treg（tTregs）也可以上调 RORγt 表达并有助于 RORγt Tregs 池的可能性在很大程度上被忽视了。在这里，我们通过证明 tTregs 也可以获得 RORγt 表达，扩展了我们对 RORγt Tregs 起源的认识。在 Foxp3 报告基因小鼠中，发现大量 CNS1 不依赖的 Tregs，主要由 tTregs 组成，共同表达 RORγt。此外，从 Foxp3RAG 报告基因小鼠的胸腺中分离出来的真正的 tTregs，无论是在体外还是体内，特别是在炎症条件下，都开始表达 RORγt。总之，我们的数据表明，tTregs 在炎症条件下可以上调 RORγt 的表达，因此 RORγt Tregs 可以被视为一个由 pTregs 和 tTregs 组成的异质群体。关键信息：RORγt 不能被视为 pTregs 的标志物。结肠中 CNS1 不依赖的 tTregs 显示出 RORγt 的表达。RORγt 可以在真正的 tTregs 中诱导，特别是在炎症条件下。RORγt Tregs 是一个由 pTregs 和 tTregs 组成的异质群体。
