Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA840855 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primarSecretory IgA (SIgA) interaction with commensal bacteria regulates the composition and function of the microbiota, contributing to gut ecosystem homeostasis. However, mechanisms regulating the reciprocal control of microbiota and SIgA are not defined. Bacteria-derived ATP limits T follicular helper (Tfh) cells activity in the Peyer’s patches (Pps) of the small intestine via the P2X7 receptor and thereby SIgA generation. Here we show that inhibition of bacteria derived ATP signaling by delivery of the ATP-degrading enzyme apyrase to the intestine results in the amplification of the SIgA repertoire. The enhanced breadth of SIgA in mice colonized with apyrase-releasing E. Coli conditioned topographical distribution of bacteria and expression of genes involved in metabolic versus immune functions in the intestinal epithelium. SIgA mediated conditioning of bacteria and enterocyte function was also reflected by selective differences in nutrients absorption in mice colonized with apyrase expressing bacteria. Hydrolysis of bacteria derived ATP was particularly helpful in restoring intestinal homeostasis via SIgA in antibiotics induced dysbiosis. Administration of apyrase expressing bacteria attenuated intestinal barrier impairment, glucose metabolism perturbation and susceptibility to infection by enteric pathogens induced by antibiotic treatments. Therefore, microbiota derived ATP regulates SIgA, and amplification of SIgA response by apyrase can be leveraged to restore intestinal fitness in dysbiotic conditions.y epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium.
2022-07-13 | GSE203433 | GEO
Project description:Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis
| PRJEB49686 | ENA
Project description:The gut microbiota is essential for many aspects of host physiology, and locally generated secretory IgA (SIgA) modulates its function. Microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy. Extracellular ATP (eATP) released by the microbiota restricts the SIgA repertoire by limiting T follicular helper (Tfh) cells activity in the Peyer’s Patches (PPs) via stimulation of ionotropic P2X7 receptor. Here we show that SIgA amplification by oral administration of the ATP hydrolysing enzyme apyrase corrects enteropathic features of ICB and improves the therapeutic outcome.
2023-12-29 | GSE250013 | GEO
Project description:The mammalian gut is inhabited by a large and complex microbial community that lives in a mutualistic relationship with its host. Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with this commensal microbiota. Secretory antibodies are generated from the active polymeric Ig receptor (pIgR)-mediated transport of IgA and IgM antibodies to the gut lumen and form the first line of adaptive immune defense of the intestinal mucosa. We probed mucosal homeostasis in pIgR knockout (KO) mice, which lack secretory antibodies. We found that in pIgR KO mice, colonic epithelial cells, the cell type most closely in contact with intestinal microbes, differentially expressed (>2-fold change) more than 200 genes compared with wild type mice, and upregulated the expression of anti-microbial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and wild type mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis, and that this was driven by their conventional intestinal microbiota. In conclusion, secretory antibodies or the pIgR itself are required to maintain a stable commensal microbiota. In the absence of these humoral effector components, gut homeostasis is disturbed and the outcome of colitis significantly worsened. 4 groups: wild type mice treated with antibiotic (5 replicates), wild type mice left untreated (5 replicates), pIgR KO mice treated with antibiotic (6 replicates), and pIgR KO mice left untreated (6 replicates).
2013-12-28 | E-GEOD-34630 | biostudies-arrayexpress
Project description:Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA
| PRJEB68326 | ENA
Project description:Maintenance of intestinal homeostasis requires a healthy relationship between the commensal gut microbiota and the host immune system. Breast milk supplies the first source of antigen-specific immune protection in the gastrointestinal tract of suckling mammals, in the form of secretory immunoglobulin A (SIgA). SIgA is transported across glandular and mucosal epithelial cells into external secretions by the polymeric immunoglobulin receptor (pIgR). Here, a breeding scheme with pIgR-sufficient and -deficient mice was used to study the effects of breast milk-derived SIgA on development of the gut microbiota and host intestinal immunity. Early exposure to maternal SIgA prevented the translocation of aerobic bacteria from the neonatal gut into draining lymph nodes, including the opportunistic pathogen Ochrobactrum anthropi. By the age of weaning, mice that received maternal SIgA in breast milk had a significantly different gut microbiota from mice that did not receive SIgA, and these differences were magnified when the mice reached adulthood. Early exposure to SIgA in breast milk resulted in a pattern of intestinal epithelial cell gene expression in adult mice that differed from that of mice that were not exposed to passive SIgA, including genes associated with intestinal inflammatory diseases in humans. Maternal SIgA was also found to ameliorate colonic damage caused by the epithelial-disrupting agent dextran sulfate sodium. These findings reveal unique mechanisms through which SIgA in breast milk may promote lifelong intestinal homeostasis, and provide additional evidence for the benefits of breastfeeding. We used microarrays to determine the effects of passive and active secretory IgA, in the presence or absence of the epithelial-disrupting agent dextran sulfate sodium, on gene expression in intestinal epithelial cells of mice A breeding scheme was used that involved crosses between mouse dams and sires that were deficient or sufficient for expression of the polymeric immunoglobulin receptor (Pigr), a protein that is required for transport of secretory IgA (SIgA) into external secretions. Offspring of these crosses were genotyped for Pigr alleles, and littermate offspring were distributed into 4 groups based on early exposure to passive SIgA in mother's milk (P-yes and P-no) and ability to carry out Pigr-mediated endogenous transport of active SIgA (A-yes and A-no). Seventy-day-old gender-matched Pigr+/- and Pigr-/- offspring of Pigr+/- and Pigr-/- dams were left untreated or given 2% dextran sulfate sodium (DSS) in drinking water for 8 days. Colonic epithelial cells were isolated, and total cellular RNA was purified. RNA was pooled from 3 mice for each of 2 biological replicates for microarray analysis.
2014-01-25 | E-GEOD-54371 | biostudies-arrayexpress
Project description:The mammalian gut is inhabited by a large and complex microbial community that lives in a mutualistic relationship with its host. Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with this commensal microbiota. Secretory antibodies are generated from the active polymeric Ig receptor (pIgR)-mediated transport of IgA and IgM antibodies to the gut lumen and form the first line of adaptive immune defense of the intestinal mucosa. We probed mucosal homeostasis in pIgR knockout (KO) mice, which lack secretory antibodies. We found that in pIgR KO mice, colonic epithelial cells, the cell type most closely in contact with intestinal microbes, differentially expressed (>2-fold change) more than 200 genes compared with wild type mice, and upregulated the expression of anti-microbial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and wild type mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis, and that this was driven by their conventional intestinal microbiota. In conclusion, secretory antibodies or the pIgR itself are required to maintain a stable commensal microbiota. In the absence of these humoral effector components, gut homeostasis is disturbed and the outcome of colitis significantly worsened.
2013-12-28 | GSE34630 | GEO
Project description:The gut microbiota is essential for many aspects of host physiology, and locally generated secretory IgA (SIgA) modulates its function. Microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy. Extracellular ATP (eATP) released by the microbiota restricts the SIgA repertoire by limiting T follicular helper (Tfh) cells activity in the Peyer’s Patches (PPs) via stimulation of ionotropic P2X7 receptor. Here we show that SIgA amplification by oral administration of the ATP hydrolysing enzyme apyrase corrects enteropathic features of ICB and improves the therapeutic outcome.
2023-12-29 | GSE250012 | GEO
Project description:Breast milk is associated with multiple benefits for the infant, including reduced incidence of chronic diseases such as Inflammatory Bowel Disease. We investigated the role of milk-derived maternal IgA (matIgA) on the developing small intestinal immune system. Using a model, where genotypically identical pups were fed by dams differed only in IgA production we revealed that matIgA regulates the assembly of the infant small intestinal microbiota and epithelium, supporting Lactobacillaceae and suppressing Enterobacteriaceae and the development of secretory lineage cells. Via the microbiota, MatIgA also regulated infant immune cells and suppressed early activation of Th17 cells. We demonstrated that Enterobacteriaceae-specific CD4+ T cells, activated in the absence of matIgA, persisted long term where they may contribute to subsequent inflammatory episodes. This work suggests that maternal IgA shapes the mucosal immune response by regulating the early-life microbiota thus preventing the development of inflammatory microbiota-specific T cells with memory potential.
2024-02-16 | GSE255576 | GEO
Project description:Krüppel-like factor 2 (KLF2) is a potent regulator of lymphocyte differentiation, activation and migration. However, its functional role in adaptive and humoral immunity remains elusive. Therefore, by using mice with a B cell-specific deletion of KLF2, we investigated plasma cell differentiation and antibody responses. We revealed that the deletion of KLF2 resulted in perturbed IgA plasma cell compartmentalization, characterized by the absence of IgA plasma cells in the bone marrow, their reductions in the spleen, the blood and the lamina propria of the colon and the small intestine, concomitant with their accumulation and retention in mesenteric lymph nodes and Peyer’s patches. Most intriguingly, secretory IgA in the intestinal lumen was almost absent, dimeric serum IgA was drastically reduced and antigen-specific IgA responses to soluble Salmonella flagellin were blunted in KLF2-deficient mice. Perturbance of IgA plasma cell localization was caused by deregulation of CCR9, Integrin chains αM, α4, β7, and sphingosine-1-phosphate receptors. Hence, KLF2 not only orchestrates the localization of IgA plasma cells by fine-tuning chemokine receptors and adhesion molecules but also controls IgA responses to Salmonella flagellin.
2022-07-13 | GSE160732 | GEO