School for Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK; Centre for Host Microbiome Interactions, King's College London, London SE1 9RT, UK; Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK; Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK; Wellcome Trust Cell Therapies and Regenerative Medicine Ph.D. Programme, London SE1 9RT, UK.
School for Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK; Centre for Host Microbiome Interactions, King's College London, London SE1 9RT, UK; Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK.
Cell Rep. 2022 Aug 30;40(9):111281. doi: 10.1016/j.celrep.2022.111281.
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, murine intestinal and pulmonary organoids are harnessed to demonstrate that the epithelial niche is sufficient to drive tissue-specific maturation of all innate lymphoid cell (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex human induced pluripotent stem cell (hiPSC)-based gut and lung organoid models are used to demonstrate that human epithelial cells recapitulate maturation of ILC from a stringent systemic human ILCP population, but only when the organoid-associated stromal cells are depleted. These systems offer versatile and reductionist models to dissect the impact of environmental and mucosal niche cues on ILC maturation. In the future, these could provide insight into how ILC activity and development might become dysregulated in chronic inflammatory diseases.
本文提出了基于类器官的鼠类和人类先天淋巴细胞前体 (ILCP) 成熟模型。首先，利用鼠类肠道和肺部类器官证明上皮细胞龛足以平行驱动所有先天淋巴细胞 (ILC) 组的组织特异性成熟，而不需要亚群特异性细胞因子补充。然后，使用更复杂的基于人诱导多能干细胞 (hiPSC) 的肠道和肺部类器官模型证明，人类上皮细胞可重现严格来源于系统性人 ILCP 群体的 ILC 成熟，但仅当类器官相关基质细胞被耗尽时才会如此。这些系统提供了灵活且简化的模型，可用于剖析环境和黏膜龛位线索对 ILC 成熟的影响。未来，这些系统可能有助于深入了解 ILC 活性和发育如何在慢性炎症性疾病中失调。
