Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance towards the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56Bright decidual ILCs, C10 and C2, that express divergent levels of Eomes. We found that decidual C10, C2, and cNKs correlated highly with previously identified first trimester decidual dNKs (dNK1-3). Functional analysis revealed polyfunctional profiles that depend on the nature of the stimulus, with a preference for IFNgamma and VEGF production. Overall, our data suggests persistence of pregnancy-specific decidual innate lymphocytes across pregnancy. Overall design: Cells of interest (C10 and C2) were isolated from 3 different decidua samples (biological replicates). As a reference, cNKs were also isolated from the same decidua samples, as they are well characterized in the literature.

成功的妊娠需要母体产生多项生理适应，包括建立对半同种异体胎儿的免疫耐受。先天淋巴样细胞（innate lymphoid cells，ILCs）在黏膜与屏障表面的免疫调控及组织稳态维持中扮演着关键角色。通过降维分析与转录组学研究，本研究鉴定出两种新型CD56Bright蜕膜ILCs——C10与C2，二者的转录因子Eomes（Eomesodermin）表达水平存在显著差异。研究发现，蜕膜C10、C2及经典自然杀伤细胞（classical natural killer cells，cNKs）与此前已鉴定的早期妊娠蜕膜自然杀伤细胞亚群（dNK1-3）具有高度相似的转录特征。功能分析结果显示，这些细胞呈现依赖刺激类型的多功能活性谱，更倾向于分泌干扰素γ（Interferon gamma，IFNγ）与血管内皮生长因子（Vascular Endothelial Growth Factor，VEGF）。总体而言，本研究数据表明，妊娠特异性蜕膜先天淋巴细胞在整个妊娠周期中持续存在。
实验设计：本研究的目标细胞（C10与C2）从3份独立蜕膜样本中分离获得（生物学重复）；作为参照，我们同时从相同蜕膜样本中分离了cNKs，因其在已有学术文献中已得到充分表征。