RORα决定胚胎胸腺中T细胞和ILC2的分化

作者：张馨予

本期文章：《自然—免疫学》：Online/在线发表

英国MRC分子生物学实验室Andrew N. J. McKenzie、Ana C. F. Ferreira研究团队的最新研究表明，RORα是胚胎胸腺中T细胞和2型先天性淋巴样细胞（ILC2）分化的关键节点。该研究于2021年1月11日发表于《自然-免疫学》杂志。

研究人员发现功能性ILC2细胞可以从胚胎胸腺共有前体T细胞中产生，早于CD4+ CD8+（双阳性）T细胞的形成。胸腺ILC2细胞迁移至粘膜组织，并在肠固有层定植。转录因子RORα的表达抑制T细胞发育的同时促进胸腺中ILC2的发育。对RNA序列、转座酶可及性染色质测序（ATAC-seq）和染色质免疫沉淀-测序（ChIP-seq）数据分析，研究人员提出了一种校正的转录途径来解释T细胞和ILC2细胞可能是由共有胸腺祖细胞发育而来。当存在Notch信号时，BCL11B会抑制Nfil3和Id2的表达，从而使E蛋白定向T细胞发挥作用。

但是，同时表达RORα解除了Nfil3和Id2的抑制作用，从而使ID2抑制E蛋白并促进ILC2分化。因此，该研究证明了RORα的表达是胚胎胸腺中T细胞和ILC2谱系分叉处的关键节点。

研究人员表示，ILC2有助于免疫稳态、保护性免疫和组织修复。

附：英文原文

Title: RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus

Author: Ana C. F. Ferreira, Aydan C. H. Szeto, Morgan W. D. Heycock, Paula A. Clark, Jennifer A. Walker, Alastair Crisp, Jillian L. Barlow, Sophie Kitching, Alfred Lim, Mayuri Gogoi, Richard Berks, Maria Daly, Helen E. Jolin, Andrew N. J. McKenzie

Issue&Volume: 2021-01-11

Abstract: Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4+CD8+ (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein–directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.

DOI: 10.1038/s41590-020-00833-w

Source: https://www.nature.com/articles/s41590-020-00833-w

期刊信息

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：23.53
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex