T-bet和RORα通过调节胚胎先天淋巴细胞分化来控制淋巴结(LN)形成，这一成果由德国风湿病研究中心柏林DRFZ莱布尼茨研究所Chiara Romagnani研究团队经过不懈努力而取得。2021年9月23日出版的《自然-免疫学》杂志发表了这项成果。

使用多个小鼠模型和胎儿先天淋巴细胞（ILC）和ILC祖细胞(ILCP)单细胞分析，研究人员确定了T-bet在胚胎发生过程中的关键作用，并表明它的缺失可以挽救RORγt缺陷小鼠中LN的形成。从机制上讲，T-bet缺失会改变胎儿ILC的分化命运，并以RORα依赖性方式促进表达中心淋巴组织诱导物 (LTi)分子的PLZFhi ILCP积累。该研究数据揭示了T-bet和RORα在胚胎ILC发育过程的特别作用，并强调RORγt在抵消T-bet抑制作用方面的重要功能。

据悉，胚胎发生过程中淋巴组织的产生依赖于第3组先天淋巴细胞(ILC3)，其具有LTi活性并表达关键转录因子RORγt。因此，RORγt缺失小鼠缺乏ILC3和淋巴结构，包括淋巴结 。尽管T-bet在个体出生后影响ILC3的分化和功能，但T-bet在调节胎儿ILC3和LN形成中的作用仍然未知。

附：英文原文

Title: T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation

Author: Stehle, Christina, Rckert, Timo, Fiancette, Rmi, Gajdasik, Dominika W., Willis, Claire, Ulbricht, Carolin, Durek, Pawel, Mashreghi, Mir-Farzin, Finke, Daniela, Hauser, Anja Erika, Withers, David R., Chang, Hyun-Dong, Zimmermann, Jakob, Romagnani, Chiara

Issue&Volume: 2021-09-23

Abstract: The generation of lymphoid tissues during embryogenesis relies on group 3 innate lymphoid cells (ILC3) displaying lymphoid tissue inducer (LTi) activity and expressing the master transcription factor RORγt. Accordingly, RORγt-deficient mice lack ILC3 and lymphoid structures, including lymph nodes (LN). Whereas T-bet affects differentiation and functions of ILC3 postnatally, the role of T-bet in regulating fetal ILC3 and LN formation remains completely unknown. Using multiple mouse models and single-cell analyses of fetal ILCs and ILC progenitors (ILCP), here we identify a key role for T-bet during embryogenesis and show that its deficiency rescues LN formation in RORγt-deficient mice. Mechanistically, T-bet deletion skews the differentiation fate of fetal ILCs and promotes the accumulation of PLZFhi ILCP expressing central LTi molecules in a RORα-dependent fashion. Our data unveil an unexpected role for T-bet and RORα during embryonic ILC function and highlight that RORγt is crucial in counteracting the suppressive effects of T-bet.

DOI: 10.1038/s41590-021-01029-6

Source: https://www.nature.com/articles/s41590-021-01029-6