Authors
Wang H J Cao, Yue You, Nancy Wang, M Zeeshan Chaudhry, Huiyang Yu, Peter T Bell, Ellesandra C Noye, Renae Denman, Byungchul Lee, Abbey Waddington, Junpeng Ye, Jaring Schreuder, Qiutong Huang, Julie Tellier, Sophie Curio, James Santiago, Daniela Amann-Zalcenstein, Nicolas Jacquelot, Peter Hickey, Stephen L Nutt, Cyril Seillet, Philip M Hansbro, Verena C Wimmer, Richard A Strugnell, Zewen Kelvin Tuong, Matthew E Richie, Gabrielle T Belz
Published in
Nature immunology. Aug 14, 2026. Epub Aug 14, 2026.
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.
PMID:
42601474
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.
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