Peyer&#39;s patch M cells organize an epithelial niche that sustains group 3 innate lymphoid cells and IL-22

Cao, WHJ; You, Y; Wang, N; Chaudhry, MZ; Yu, H; Bell, PT; Noye, EC; Denman, R; Lee, B; Waddington, A; Ye, J; Schreuder, J; Huang, Q; Tellier, J; Curio, S; Santiago, J; Amann-Zalcenstein, D; Jacquelot, N; Hickey, P; Nutt, SL; Seillet, C; Hansbro, PM; Wimmer, VC; Strugnell, RA; Tuong, ZK; Richie, ME; Belz, GT

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

Author(s): Cao, WHJ; You, Y; Wang, N; Chaudhry, MZ; Yu, H; Bell, PT; Noye, EC; Denman, R; Lee, B; Waddington, A; Ye, J; Schreuder, J; Huang, Q; Tellier, J; Curio, S; Santiago, J; Amann-Zalcenstein, D; Jacquelot, N; Hickey, P; Nutt, SL; Seillet, C; Hansbro, PM; Wimmer, VC; Strugnell, RA; Tuong, ZK; Richie, ME; Belz, GT;
Details: Publication Year 2026-09,Volume 27,Issue #9,Page 1829-1841
Journal Title: Nature Immunology
Publication Type: Aug 14
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 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.
Publisher: Springer Nature
Keywords: Animals; Interleukin-22; *Interleukins/metabolism/immunology; *Immunity, Innate; *Peyer's Patches/immunology/cytology; Mice; *Lymphocytes/immunology; Receptors, CCR6/metabolism; *M Cells/immunology/metabolism; *Intestinal Mucosa/immunology; Immunity, Mucosal; Mice, Inbred C57BL; Mice, Knockout; Epithelial Cells/immunology; Signal Transduction; Cell Proliferation; Immunoglobulin A/immunology/metabolism
Research Division(s): Immunology; Advanced Technology and Biology; Personalised Oncology; Genetics and Gene Regulation
PubMed ID: 42601474
Publisher's Version: https://doi.org/10.1038/s41590-026-02606-3
Open Access at Publisher's Site: https://doi.org/10.1038/s41590-026-02606-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-08-28 10:52:03

Last Modified: 2026-08-28 10:56:27