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Shaping Gut Immunity with Intestinal Epithelial-Immune Dynamics in Peyer's Patches.

ABSTRACT: Microfold (M) cells are specialized antigen-sampling cells that transcytose luminal antigens to underlying immune cells to initiate mucosal immunity. How they are programmed in different intestinal tissues and their role during enteric infections has not been resolved. Here, we demonstrate that M cells are critical for B cell activation and IgA production that shapes the intestinal microbiome and maintains steady-state intestinal epithelial integrity. Tuft cells and M cells share expression of SPI-B. Molecular mapping revealed that M cells exhibit significant heterogeneity including tissue-specific and pathogen-specific tailored programs. These include key pathways regulating fatty acid uptake and metabolism in the intestinal epithelium. Confocal imaging demonstrated that Peyer’s patch SPI-B+ M cells act to retain group 3 innate lymphoid cells and IL-22 production within the Peyer's patch epithelium. By identifying interconnected cellular and molecular programs, we uncover novel spatially organized immune-epithelial regulatory networks essential for immune protection.

ORGANISM(S): Mus musculus

PROVIDER: GSE280531 | GEO | 2026/06/29

REPOSITORIES: GEO

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Project description:M cells in the follicle-associated epithelium (FAE) of Peyer’s patches (PPs) serve as a main portal for external antigens. Limitation in the number of M cells has hampered identification of their specific molecules until recently. Efforts by us as well as others has gradually unraveled the molecular mechanisms for the development and differentiation of M cells. However, molecular mechanisms of antigen transcytosis and M cell differentiation were not fully elucidated. Recent studies reported that small non-coding RNAs including microRNA (miRNA) regulate gene expression that controls various biological processes such as cellular differentiation and functions. In fact, intestinal epithelial miRNAs play a critical role in goblet cell differentiation and maturation. However, the expression and function of miRNAs in FAE including M cell that function as the sentinels in the mucosal immune system are largely unknown. To address this notion, we performed microarray analysis to characterize expression profiles of miRNA in intestinal villous epithelium (VE) and FAE of PP. We also generated mice with intestinal epithelial cell-specific deletion of Dicer1 (DicerΔIEC), in which intestinal phenotypes including M-cell differentiation and epithelial morphology were examined. The microarray analysis identified that 72 miRNAs were up-regulated whereas 11 miRNAs were down-regulated, in FAE compared to VE. DicerΔIEC mice displayed a prominent decrease in mature M cells, suggesting an essential role of miRNAs in maturation of the cell type. Furthermore, electron micrographs clearly showed that depletion of miRNA caused the loss of endosomal structures in M cells. In addition, antigen uptake in M cells was impaired in DicerΔIEC mice compared to control floxed Dicer mice. These results raised the possibility that miRNAs play a significant role in the regulation of M cells maturation, and consequently secure mucosal immune homeostasis. Follicle associated epithelium or villous epithelium was isolated from Peyer's patch(PP). PP was soaked Hank's balanced salt solution (HBSS;GIBCO) containing 30mM EDTA. After incubation at 4℃ for 20 min, FAE or VE was isolated by manipulation with fine needle under stereomicroscopic monitoring. The isolated epithelial cell sheets were kept in ice-cold HBSS until RNA extraction(n=2).

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Shaping Gut Immunity with Intestinal Epithelial-Immune Dynamics in Peyer's Patches.

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