Immunology Research Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy.
Immunology Operative Unit, Department of Integrated Oncological Therapies, IRCCS Policlinico San Martino Hospital, Genoa, Italy.
Front Immunol. 2020 Feb 6;11:133. doi: 10.3389/fimmu.2020.00133. eCollection 2020.
Innate lymphoid cells (ILCs) are a heterogeneous subset of lymphocytes deeply implicated in the innate immune responses to different pathogens, in lymphoid organogenesis and in the maintenance of tissue homeostasis. Group 3 innate lymphoid cells (ILC3) have been detected in human decidua, where they play a role in the early inflammatory phase favoring implantation and tissue remodeling as well as in the subsequent regulatory phase preventing fetal rejection and supporting neoangiogenesis. A balance between inflammation and immune tolerance is required to maintain pregnancy, thus maternal immune system must be controlled by finely tuned mechanisms. microRNAs (miRNAs) are small non-coding RNAs with important regulatory roles in immune cells, but their function in decidual ILC3 (dILC3) and in decidual NK (dNK) cells is still undefined. Here, we examined the miRNome by microarray in these cells during the first trimester of pregnancy and compared with miRNA profiles of peripheral blood NK (pbNK) cells from pregnant women. We show that distinct miRNA profiles could clearly distinguish dILC3 from NK cells. Correlation analyses revealed that dNK and pbNK miRNome profiles are more similar to each other as compared to dILC3. In particular, we identified 302 and 279 mature miRNAs differentially expressed in dILC3 as compared to dNK and pbNK, respectively. The expression of and the miRNA cluster resulted the most increased in dILC3. Remarkably, gene ontology analysis and pathway enrichments of miRNA targets revealed an involvement of these miRNAs in the promotion of anti-inflammatory responses. In agreement to this finding, we also found a higher expression of the anti-inflammatory in dILC3 with respect to NK cells. Overall, our data identified specific miRNA signatures distinguishing dILC3, dNK, and pbNK cells. Our data suggest the existence of a tight epigenetic control mediated by miRNAs in dILC3, potentially acting as a brake to prevent exaggerated inflammatory responses and to maintain the immune homeostasis in the early phases of pregnancy.
固有淋巴细胞（ILC）是淋巴细胞的一个异质性亚群，它们在对不同病原体的固有免疫反应、淋巴器官发生和组织内稳态的维持中起着重要作用。在人类蜕膜中已经检测到了第 3 组固有淋巴细胞（ILC3），它们在促进着床和组织重塑的早期炎症阶段以及随后的免疫调节阶段发挥作用，以防止胎儿排斥和支持新血管生成。为了维持妊娠，需要在炎症和免疫耐受之间取得平衡，因此母体免疫系统必须受到精细调控机制的控制。微小 RNA（miRNA）是具有重要免疫细胞调节作用的小非编码 RNA，但它们在蜕膜固有淋巴细胞（dILC3）和蜕膜自然杀伤（dNK）细胞中的功能仍未确定。在这里，我们通过微阵列分析了这些细胞在妊娠早期的 miRNome，并与来自孕妇的外周血 NK（pbNK）细胞的 miRNA 谱进行了比较。我们表明，独特的 miRNA 谱可以清楚地区分 dILC3 和 NK 细胞。相关性分析表明，与 dILC3 相比，dNK 和 pbNK 的 miRNome 谱更为相似。特别是，我们发现与 dNK 和 pbNK 相比，dILC3 中有 302 个和 279 个成熟 miRNA 表达差异。在 dILC3 中表达最上调的是 和 miRNA 簇。值得注意的是，miRNA 靶基因的功能分析和通路富集分析表明，这些 miRNA 参与了促炎反应的抑制。与这一发现一致，我们还发现与 NK 细胞相比，dILC3 中抗炎因子 的表达更高。总的来说，我们的数据确定了区分 dILC3、dNK 和 pbNK 细胞的特异性 miRNA 特征。我们的数据表明，dILC3 中存在由 miRNA 介导的严格的表观遗传控制，这可能作为一种刹车，以防止过度的炎症反应，并在妊娠的早期阶段维持免疫内稳态。
