Shih Han-Yu, Sciumè Giuseppe, Mikami Yohei, Guo Liying, Sun Hong-Wei, Brooks Stephen R, Urban Joseph F, Davis Fred P, Kanno Yuka, O'Shea John J
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell. 2016 May 19;165(5):1120-1133. doi: 10.1016/j.cell.2016.04.029. Epub 2016 May 5.
Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4(+) T helper (Th) cell subtypes in both usage of effector molecules and transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4(+) T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways.
固有淋巴细胞（ILCs）在宿主防御、屏障完整性和内环境稳态中发挥关键作用，并且在效应分子和转录因子的使用上反映了适应性CD4(+)辅助性T（Th）细胞亚型。为了更好地理解ILC亚群与其对应的Th细胞之间的关系，我们测量了全基因组染色质可及性。我们发现，在激活后高水平转录之前，ILCs中靠近效应基因的染色质是选择性可及的。这些区域的可及性在发育过程中逐步获得，并且在体外或体内激活后变化很小。相反，在使用2型感染模型的Th细胞分化过程中，初始CD4(+) T细胞会发生显著的染色质重塑。这种改变导致Th2细胞在调控基因组方面与ILC2大量趋同。我们的数据表明，尽管免疫系统的固有和适应性部分发育途径不同，但它们在调控回路方面存在广泛共享。
