Organoids capture tissue-specific innate lymphoid cell development in mice and humans

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.

Automated summary

This article presents organoid-based models for studying the maturation of murine and human innate lymphoid cell precursors (ILCPs). The results show that the epithelial niche is sufficient to drive tissue-specific maturation of all ILC groups in mice, and human epithelial cells can recapitulate ILC maturation in the absence of organoid-associated stromal cells. These models provide a versatile approach to investigate the impact of environmental and mucosal factors on ILC maturation.