Gut-associated lymphoid tissues (GALTs) are critical for orchestrating local immune responses. Our understanding of these structures has mostly come from studies in mice. However, the relevance of these findings to human GALT formation is unclear. Using single-cell RNA sequencing we map cellular landscapes of healthy human developing, pediatric and adult intestines and pediatric Crohn's disease. From this comprehensive dataset of almost half a million cells we investigate GALTs and uncover fine-scale cellular mechanisms leading to their formation.
We characterise the main cellular mechanisms in GALT formation describing novel developmental cell subtypes not observed in animal models, suggesting possible species differences. Applying spatially-resolved transcriptomics we place these cell types within the tissue context of emerging GALTs and highlight recruitment of immune cells to these sites. Additionally, we find that expanded populations of cells in pediatric Crohn’s disease have equivalent signatures to those in GALT development, implying that readaptation of developmental programs may drive chronic inflammation. Together, this work provides an unprecedented catalogue of intestinal cells, identifying novel cell types and interactions with potential therapeutic value for treatment of gut inflammatory diseases.