Peyer’s patch M cells organize an epithelial niche that sustains group 3 innate lymphoid cells and IL-22

Abstract

Microfold (M) cells transcytose luminal antigens to initiate mucosal adaptive immunity, but their role in organizing innate responses in Peyer’s patches is unclear. Here we showed that Peyer’s patch M cells organized an epithelial–group 3 innate lymphoid cell (ILC3) axis, establishing a spatial niche within the dome epithelium that drove ILC3 localization, proliferation and IL-22 production. We found that epithelial, but not hematopoietic, SPI-B was required for intestinal IgA responses to establish this niche. Single-cell profiling of intestinal SPI-B+ epithelial cells revealed that M cells were highly heterogeneous, displaying tissue- and pathogen-specific transcriptional programs. Using s..