Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1303991 | ENA |
REPOSITORIES: ENA
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Project description:Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease (IBD) and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype, i.e., they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared to wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CTB-specific serum IgG response in C57BL/6.IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria (SFB) in the small intestine of C57BL/6.IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by SFB but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expressions of a panel of immune regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a non-pathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.
2017-08-31 | GSE97571 | GEO
Project description:Bifidobacteria is strongly associated with human health and dominates the gut microbiota of breast-fed infants. However, Bifidobacteria persists at high abundance in only a subset of individuals after weaning, and the factors that regulate intestinal persistence of Bifidobacteria are poorly understood. Here, we identified that a common dietary fiber, raffinose, supports Bifidobacteria persistence within complex microbiome communities. Raffinose-driven Bifidobacteria persistence is associated with disease resistance and restrained inflammation in mice. Altogether, our findings show that raffinose selectively regulates the intestinal persistence of Bifidobacteria, which may enable its sustained maintenance during microbiome diversification and thereby support prolonged probiotic functions.
2026-08-31 | GSE330841 | GEO
Project description:Bifidobacteria is strongly associated with human health and dominates the gut microbiota of breast-fed infants. However, Bifidobacteria persists at high abundance in only a subset of individuals after weaning, and the factors that regulate intestinal persistence of Bifidobacteria are poorly understood. Here, we identified that a common dietary fiber, raffinose, supports Bifidobacteria persistence within complex microbiome communities. Raffinose-driven Bifidobacteria persistence is associated with disease resistance and restrained inflammation in mice. Altogether, our findings show that raffinose selectively regulates the intestinal persistence of Bifidobacteria, which may enable its sustained maintenance during microbiome diversification and thereby support prolonged probiotic functions.
2026-08-31 | GSE330259 | GEO
Project description:Bifidobacteria is strongly associated with human health and dominates the gut microbiota of breast-fed infants. However, Bifidobacteria persists at high abundance in only a subset of individuals after weaning, and the factors that regulate intestinal persistence of Bifidobacteria are poorly understood. Here, we identified that a common dietary fiber, raffinose, supports Bifidobacteria persistence within complex microbiome communities. Raffinose-driven Bifidobacteria persistence is associated with disease resistance and restrained inflammation in mice. Altogether, our findings show that raffinose selectively regulates the intestinal persistence of Bifidobacteria, which may enable its sustained maintenance during microbiome diversification and thereby support prolonged probiotic functions.
2026-08-31 | GSE330838 | GEO
Project description:The mechanisms whereby enteric pathogens and microbes induce systemic antibody responses remain obscure. In contrast to accepted models, we show that commensal microbes have a dramatic impact on the bone marrow (BM) plasma cell pool. Unlike standard vendor mice, in mice reared in our colony the majority of long-lived BM plasma cells secreted IgA antibodies. Exposing vendor mice to a unique microflora or Helicobacter sp. led to the generation of IgA-secreting BM cells, while also inducing increases in serum IgA antibodies enriched for binding to several commensal bacterial taxa. Moreover, BM IgA-secreting plasma cells exhibited a common clonal ancestry with intestinal IgA+ plasma cells, and both populations possessed unique gene expression signatures compared to other long-lived BM plasma cells. We conclude that commensal microbes overtly influence the BM plasma cell pool, and suggest that select commensal microbes can facilitate the induction of systemic humoral immunity.
2018-07-01 | GSE87091 | GEO
Project description:Redundant mechanisms support IgA responses to intestinal antigens. These include multiple priming sites (mesenteric lymph nodes (MLN), Peyer's patches and isolated lymphoid follicles) and various cytokines that promote class switch to IgA, even in the absence of T cells. In spite of these back-up mechanisms, vaccination against enteric pathogens such as Rotavirus has limited success in some populations.Genetic and environmental signals experienced during early life are known to influence mucosal immunity, yet the mechanisms for how these exposures operate remain unclear. Here we used Rotavirus infection to follow antigen-specific IgA responses through time and in different gut compartments. Using genetic and pharmacological approaches, we tested the role of a pathway known to support IgA responses (Lymphotoxin - LT) at different developmental stages. We found that LT-beta receptor (LTβR) signalling in early life programs intestinal IgA responses in adulthood by affecting antibody class switch recombination to IgA and subsequent generation of IgA antibody-secreting cells within an intact MLN. In addition, early life LTβR signalling dictates the phenotype and function of MLN stromal cells in order to support IgA responses in the adult. Collectively, our studies uncover new mechanistic insights into how early life LTβR signalling impacts mucosal immune responses during adulthood.
2019-10-05 | GSE138455 | GEO
Project description:Redundant mechanisms support IgA responses to intestinal antigens. These include multiple priming sites (mesenteric lymph nodes (MLN), Peyer's patches and isolated lymphoid follicles) and various cytokines that promote class switch to IgA, even in the absence of T cells. In spite of these back-up mechanisms, vaccination against enteric pathogens such as Rotavirus has limited success in some populations.Genetic and environmental signals experienced during early life are known to influence mucosal immunity, yet the mechanisms for how these exposures operate remain unclear. Here we used Rotavirus infection to follow antigen-specific IgA responses through time and in different gut compartments. Using genetic and pharmacological approaches, we tested the role of a pathway known to support IgA responses (Lymphotoxin - LT) at different developmental stages. We found that LT-beta receptor (LTβR) signalling in early life programs intestinal IgA responses in adulthood by affecting antibody class switch recombination to IgA and subsequent generation of IgA antibody-secreting cells within an intact MLN. In addition, early life LTβR signalling dictates the phenotype and function of MLN stromal cells in order to support IgA responses in the adult. Collectively, our studies uncover new mechanistic insights into how early life LTβR signalling impacts mucosal immune responses during adulthood.
2019-10-05 | GSE138456 | GEO
Project description:Gut-educated IgA-secreting plasma cells that disseminate beyond the mucosa and into systemic tissues can help prevent disease in several contexts. Here we show, the commensal bacteria Bacteroides fragilis (Bf), is an efficient inducer of systemic IgA responses. The generation of bone marrow IgA plasma cells and high levels of serum IgA specific to Bf requires robust intestinal colonization. Bf-specific IgA responses were severely diminished in mice lacking Peyer’s patches, but not mice lacking a cecal patch. Colonization resulted in few changes in the host transcriptional profile in the gut, suggesting a commensal relationship. High levels of Bf-specific serum IgA, but not IgG, provided protection from peritoneal abscess formation in a bowel perforation model of Bf dissemination. These findings demonstrate a critical role for bacterial colonization and Peyer’s patches in the induction of robust systemic IgA responses that confer protection from bacterial dissemination originating from the gut.
2024-07-25 | GSE272717 | GEO
Project description:Dissecting the Clonal Composition and Determinants of Neutralization Potency Enhancement of Circulating Dimeric and Monomeric IgA to Human Norovirus
2026-07-09 | PXD066704 | Pride
Project description:Immunoglobulin A (IgA) is the predominant immunoglobulin isotype in mammals, primarily secreted at type I mucosal surfaces. Despite its abundance, the precise role of secretory IgA in the intestinal lumen, where it coats a diverse array of commensal microbiota, has remained elusive. Our study reveals that germinal center IgA responses are essential for preventing chronic colonization of the gut by specific viruses. In absence of IgA, chronic viral colonization triggers an antigen-driven expansion of CD8αβ+ intraepithelial lymphocytes (IELs). Although, these IELs are unable to clear the virus, they contribute to maintaining homeostasis by regulating its load and type-I interferon responses. Consequently, IgA deficiency increases susceptibility to colitis in genetically susceptible host or following chemical induction, but only in presence of viral pathobionts requiring IgA for their clearance. These findings underscore the potential vulnerability of IgA deficient individuals to immunopathology when exposed to selective viral pathobionts.
2025-03-24 | GSE289917 | GEO