Early human lung immune cell development and its role in epithelial cell fate

Early human lung immune cell development and its role in epithelial cell fate
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早期人肺免疫细胞发育及其在上皮细胞命运中的作用

DOI:
10.1101/2022.12.13.519713
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Barnes J
Barnes J
中科院分区:
--
文献类型:
--
作者:
Barnes J

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人类肺发育的研究主要集中在上皮细胞和间充质细胞的类型和功能上,但对肺免疫细胞的发育知之甚少,尽管气道是出生后粘膜免疫的主要部位。一个悬而未决的问题是,组织常驻免疫细胞是否在子宫内发育的组织塑造中发挥作用。在这里,我们使用scRNA-seq, smFISH和免疫组织化学分析了人胚胎和胎儿肺免疫细胞。在胚胎阶段,我们观察到先天免疫细胞的早期浪潮,包括先天淋巴样细胞、自然杀伤细胞、骨髓细胞和谱系祖细胞。在小管期,我们检测到表达高水平细胞毒性基因的幼稚T淋巴细胞和成熟B淋巴细胞的存在,包括B-1细胞。我们的分析表明,胎儿肺为B细胞的完全成熟提供了一个生态位。鉴于免疫细胞在发育过程中的存在和多样性,我们也研究了它们对上皮成熟的可能影响。我们发现IL-1β在体外驱动上皮祖细胞从自我更新和分化到基底细胞。在体内,产生il -1β的髓样细胞遍布肺部和上皮尖端附近,表明免疫细胞可能指导人肺上皮的发育。
Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β–producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.
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