RORα決定胚胎胸腺中T細胞和ILC2的分化
作者：
小柯機器人發布時間：2021/1/12 16:47:45
英國MRC分子生物學實驗室Andrew N. J. McKenzie、Ana C. F. Ferreira研究團隊的最新研究表明，RORα是胚胎胸腺中T細胞和2型先天性淋巴樣細胞（ILC2）分化的關鍵節點。該研究於2021年1月11日發表於《自然-免疫學》雜誌。
研究人員發現功能性ILC2細胞可以從胚胎胸腺共有前體T細胞中產生，早於CD4+ CD8+（雙陽性）T細胞的形成。胸腺ILC2細胞遷移至黏膜組織，並在腸固有層定植。轉錄因子RORα的表達抑制T細胞發育的同時促進胸腺中ILC2的發育。對RNA序列、轉座酶可及性染色質測序（ATAC-seq）和染色質免疫沉澱-測序（ChIP-seq）數據分析，研究人員提出了一種校正的轉錄途徑來解釋T細胞和ILC2細胞可能是由共有胸腺祖細胞發育而來。當存在Notch信號時，BCL11B會抑制Nfil3和Id2的表達，從而使E蛋白定向T細胞發揮作用。
但是，同時表達RORα解除了Nfil3和Id2的抑制作用，從而使ID2抑制E蛋白並促進ILC2分化。因此，該研究證明了RORα的表達是胚胎胸腺中T細胞和ILC2譜系分叉處的關鍵節點。
研究人員表示，ILC2有助於免疫穩態、保護性免疫和組織修復。
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