M cells are responsible for uptake of mucosal antigens in Peyer's patches (PPs). Differentiation of M cells is thought to be induced by interactions between follicle-associated epithelium and PP ...cells; however, it remains elusive what types of immune cells function as M-cell inducers. Here, we attempted to identify the cells that serve as an M-cell inducer in PP. We found that a unique B-cell subset characterized by CCR6 super(hi)CD11c super(int)resided in the subepithelial dome (SED) in mouse PP. CCR6 super(hi)CD11c super(int)B cells showed chemotactic migration in response to CCL20. Furthermore, this unique B-cell subset substantially decreased in PP of CCR6-deficient mice, indicating that the SED localization of CCR6 super(hi)CD11c super(int) B cells is most likely regulated by the CCL20-CCR6 system. Concomitantly, CCR6 deficiency caused remarkable decrement of M cells. Moreover, adoptive transfer of CCR6 super(hi)CD11c super(int)B cells from wild-type mice restored the M-cell decrement in CCR6-deficient mice. Collectively, the spatial regulation of CCR6 super(hi)CD11c super(int)B cells via the CCL20-CCR6 system may play a vital role in M-cell differentiation in mice.
The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium. Using ...a meta-analysis approach, we identified a transcriptional signature that distinguished the FAE from a large collection of mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was identified, and the analysis of the transcription factor binding site motifs in their promoter regions indicated that these genes shared an underlying transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20, Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were novel FAE-specific genes. Some of these novel candidate genes were expressed highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). We also identified a subset of novel FAE-related genes that were induced in the intestinal epithelium after receptor activator of nuclear factor (NF)-κB ligand stimulation. These included Mfge8 which was specific to FAE enterocytes. This study provides new insight into the FAE transcriptome. Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.
Both aging and diet play an important role in influencing the gut ecosystem. Using premature senescent rats induced by
d
-galactose and fed with high-fat diet, this study aims to investigate the ...effects of different potential probiotic strains on the dynamic changes of fecal microbiome and metabolites. In this study, male Sprague–Dawley rats were fed with high-fat diet and injected with
d
-galactose for 12 weeks to induce aging. The effect of
Lactobacillus plantarum
DR7,
L. fermentum
DR9, and
L. reuteri
8513d administration on the fecal microbiota profile, short-chain fatty acids, and water-soluble compounds were analyzed. It was found that the administration of the selected strains altered the gut microbiota diversity and composition, even at the phylum level. The fecal short-chain fatty acid content was also higher in groups that were administered with the potential probiotic strains. Analysis of the fecal water-soluble metabolites revealed that administration of
L. plantarum
DR7 and
L. reuteri
8513d led to higher fecal content of compounds related to amino acid metabolism such as tryptophan, leucine, tyrosine, cysteine, methionine, valine, and lysine; while administration of
L. fermentum
DR9 led to higher prevalence of compounds related to carbohydrate metabolism such as erythritol, xylitol, and arabitol. In conclusion, it was observed that different strains of lactobacilli can cause difference alteration in the gut microbiota and the metabolites, suggesting the urgency to explore the specific metabolic impact of specific strains on the host.
Both aging and diet play an important role in influencing the gut ecosystem. Using premature senescent rats induced by D-galactose and fed with high-fat diet, this study aims to investigate the ...effects of different potential probiotic strains on the dynamic changes of fecal microbiome and metabolites. In this study, male Sprague-Dawley rats were fed with high-fat diet and injected with D-galactose for 12 weeks to induce aging. The effect of Lactobacillus plantarum DR7, L. fermentum DR9, and L. reuteri 8513d administration on the fecal microbiota profile, short-chain fatty acids, and water-soluble compounds were analyzed. It was found that the administration of the selected strains altered the gut microbiota diversity and composition, even at the phylum level. The fecal short-chain fatty acid content was also higher in groups that were administered with the potential probiotic strains. Analysis of the fecal water-soluble metabolites revealed that administration of L. plantarum DR7 and L. reuteri 8513d led to higher fecal content of compounds related to amino acid metabolism such as tryptophan, leucine, tyrosine, cysteine, methionine, valine, and lysine; while administration of L. fermentum DR9 led to higher prevalence of compounds related to carbohydrate metabolism such as erythritol, xylitol, and arabitol. In conclusion, it was observed that different strains of lactobacilli can cause difference alteration in the gut microbiota and the metabolites, suggesting the urgency to explore the specific metabolic impact of specific strains on the host.
The endocytic and secretory pathways of eukaryotic cells consist of an array of membrane-bound compartments, each of which contains a characteristic cohort of transmembrane proteins. Understanding ...how these proteins are targeted to and maintained within their appropriate compartments will be crucial for unravelling the mysteries of organelle biogenesis and function. A common event in the sorting of many transmembrane proteins is the interaction between a sorting signal in the cytosolic domain of the targeted protein and a component of an organellar protein coat. Here, we summarize recent findings on the mechanism of sorting by one type of signal, characterized by the presence of a critical tyrosine (Y) residue, and attempt to integrate these findings into a hypothetical model for protein sorting in the endocytic and late (post-Golgi) secretory pathways.
Follicle-associated epithelium (FAE) covering Peyer's patches contains specialized epithelial M cells that take up ingested macromolecules and microorganisms from the lumen of the gut by ...transcytosis. Using high-density oligonucleotide microarrays, we analyzed the gene expression profiles of FAE and M cells in order to characterize their cellular phenotypes. The microarray data revealed that, among approximately 14,000 genes, 409 were expressed in FAE at twofold or higher levels compared to the intestinal epithelial cells (IECs) of the villi. These included genes involved in membrane traffic, host defense and transcriptional regulation, as well as uncharacterized genes. Real-time PCR and in situ hybridization analyses identified three molecules, ubiquitin D (Ub-D), tumor necrosis factor receptor superfamily 12a (TNFRsf12a), and transmembrane 4 superfamily 4 (Tm4sf4), which were predominantly distributed throughout FAE, but were expressed little, if at all, in IECs. By contrast, transcripts of secretory granule neuroendocrine protein 1 (Sgne-1) were scattered in FAE, and were co-localized with Ulex europaeus agglutinin-1 (UEA-1)-positive cells. This clearly suggests that expression of Sgne-1 in the gut is specific to M cells. Such a unique pattern of gene expression distinguishes FAE and M cells from IECs, and may reflect their cellular phenotype(s) associated with specific functional features.
Background: S‐Adenosylmethionine decarboxylase (AdoMetDC) is one of the key enzymes involved in the biosynthesis of spermidine and spermine, which are essential for normal cell growth. To examine the ...role of polyamines in embryogenesis, we carried out targeted disruption of the mouse Amd1 gene, encoding AdoMetDC, to generate mice that can not synthesize spermidine and spermine.
Results: Amd1 heterozygous mice were viable, normal and fertile. However, homozygous Amd1−/− embryos died early in embryonic development, between E3.5 and E6.5 days post‐coitus. Homozygous (Amd1−/−) blastocysts at E3.5 arrested cell proliferation immediately after the onset of cell culture, and this arrest was rescued by the addition of spermidine. Chromosomal DNA breakage did not occur in Amd1−/− blastocysts at E3.5, as determined by TUNEL assay.
Conclusions: These results indicate that AdoMetDC plays an essential role in embryonic development and that polyamines are required for cell proliferation in the embryo after E3.5.
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