美国宾夕法尼亚大学Jorge Henao-Mejia和Golnaz Vahedi小组合作取得一项新成果。他们发现基因组多尺度三维（3D）组织是ILC2产生和过敏性气道炎发生的基础。该项研究成果发表在2022年9月1日出版的《自然—免疫学》上。

研究人员对成熟先天淋巴细胞(ILC)中的3D基因组结构、染色质可及性和基因表达进行了综合分析。研究结果表明，基因组的局部3D结构在与ILC生物学相关的基因座上发生重新连接，以促进它们的发育和功能分化。重要的是，研究证明了ILC2的产生和过敏性气道炎的进展，是由包含ILC谱系决定因子Id2区域的独特局部3D结构所决定，其特征是Id2启动子和远端调节之间的多重相互作用由转录因子GATA-3和RORα结合元素决定，表明Id2在第2组ILC中的表达受到特异性调控。

据悉，ILC是特征鲜明的免疫细胞，在宿主防御和组织稳态过程中发挥关键作用。然而，基因组3D组织促进ILC产生和功能的机制尚不清楚。

附：英文原文

Title: Multiscale 3D genome organization underlies ILC2 ontogenesis and allergic airway inflammation

Author: Michieletto, Michal F., Tello-Cajiao, John J., Mowel, Walter K., Chandra, Aditi, Yoon, Sora, Joannas, Leonel, Clark, Megan L., Jimenez, Monica T., Wright, Jasmine M., Lundgren, Patrick, Williams, Adam, Thaiss, Christoph A., Vahedi, Golnaz, Henao-Mejia, Jorge

Issue&Volume: 2022-09-01

Abstract: Innate lymphoid cells (ILCs) are well-characterized immune cells that play key roles in host defense and tissue homeostasis. Yet, how the three-dimensional (3D) genome organization underlies the development and functions of ILCs is unknown. Herein, we carried out an integrative analysis of the 3D genome structure, chromatin accessibility and gene expression in mature ILCs. Our results revealed that the local 3D configuration of the genome is rewired specifically at loci associated with ILC biology to promote their development and functional differentiation. Importantly, we demonstrated that the ontogenesis of ILC2s and the progression of allergic airway inflammation are determined by a unique local 3D configuration of the region containing the ILC-lineage-defining factor Id2, which is characterized by multiple interactions between the Id2 promoter and distal regulatory elements bound by the transcription factors GATA-3 and RORα, unveiling the mechanism whereby the Id2 expression is specifically controlled in group 2 ILCs.

DOI: 10.1038/s41590-022-01295-y

Source: https://www.nature.com/articles/s41590-022-01295-y