GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE280nnn/GSE280744/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE280744GEOGSEfalsePeyer’s patch M cells organize an epithelial niche that sustains group 3 innate lymphoid cells and IL-22Microfold (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 subset-specific genetic perturbation and whole-mount imaging, we found that this circuit relied on CCR6-dependent positioning cues and RANK-RANKL signaling to ILC3 to regulate Peyer's patch ILC3 homeostasis. Together, these findings identified Peyer's patch M cells as organizers that spatially coordinated innate cell localization, proliferation and cytokine production to maintain mucosal barrier defense.2026/06/26GSE280744GSM8599882GSM8599881GSM7790630GSM7790634GSM7790633GSM7790632GSM7790631GSM7790627GSM7790626GSM7790636GSM7790625GSM7790635GSM7790629GSM77906281905730172280744Mus musculus[42601474]