Microbiota-derived butyrate alleviates asthma via constraining Tfh13-mediated IgE production.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE252579 | GEO | 2025/05/07
REPOSITORIES: GEO
Similar Datasets
Project description:Microbiota-derived butyrate alleviates asthma via constraining Tfh13-mediated IgE production.
| PRJNA1061249 | ENA
Project description:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile. The study consisted of a total of 872 sera samples: 485 individuals were diagnosed with asthma, 342 were classified as non asthmatic, a remaining 45 were classified as unconfirmed asthma diagnosis. The serum IgE reactivity profiles were analyzed against 103 allergens representative of 11 distinct allergen classes. Quantification of bound IgE: The fluorescence signal was acquired using ProScanArray Express™ version 3.0 software. PMC reading values of individual spots were corrected against the internal negative control to identify signals above background. Duplicate measurements of individual allergens were utilized. The signal collected from the allergens was interpolated with an external calibration curve to obtain the IU/ml value (see supplementary file GSE20020_IU_ml values.txt), and translated into a Class Score by plotting the data in a standard reactivity scale (see Sample data tables). Class Score values: (CLASS 0 (less than 0.35 IU/ml); CLASS 1 (0.35-0.7 IU/ml); CLASS 2 (0.71-3.5 IU/ml); CLASS 3 (3.51-17.5 IU/ml); CLASS 4 (17.51-50 IU/ml); CLASS 5 (50.01-100 IU/ml).
2012-01-03 | E-GEOD-20020 | biostudies-arrayexpress
Project description:Background: Most asthmatic patients have high serum levels of IgE directed against common environmental allergens such as house dust mite, animal danders and moulds. However the presence of specific IgE against individual allergens alone does not account for asthma. Many individuals are atopic but not asthmatic. Precise knowledge of the serum IgE specificity repertoire in asthmatic and non-asthmatic patients would substantially help in understanding the pathogenesis of the disease and at the same time facilitate the treatment and the implementation of preventive measures. Methods: We developed a microarray immunoassay containing 103 common allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals from families whose members had a documented history of asthma and atopy. The results were analyzed using k-means clustering to investigate whether IgE reactivity profiles correlated with asthma, disease severity and age of onset as well as with other atopic conditions such as rhinitis, conjunctivitis and eczema. We trained an artificial neural network (ANN) using the serum reactivity data to identify individuals as asthmatic and non-asthmatic. Results: Individual sera showed clear differences in the number and the combinations of allergens recognized as well as in the level of specific IgE. While the presence of specific IgE against single allergens correlated poorly with the pathological conditions examined k-means clustering analysis unraveled that a particular profile was significantly associated with asthma (p <1E-8). An ANN-based algorithm, calibrated with the profile reactivity data correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Conclusions: Our analysis demonstrates that asthma may be a higher-order phenomenon related to patterns of response and not attributable to single antibody reactions. This information sheds new light on the risk of developing the disease and can be readily utilized in combination with an ANN-based tool to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.
2012-01-03 | GSE20020 | GEO
Project description:Soil clostridia species metabolism for butyrate production
2024-12-05 | MSV000096601 | MassIVE
Project description:Allergy is one of the most prevalent chronic diseases, affecting hundreds of millions of people worldwide. In allergy, environmental allergens induce B cells to undergo class switch recombination and produce Immunoglobulin E (IgE) antibodies. IgE is a key molecule that mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of exogenous allergens, yet the origin, regulation, and functions of such “natural” IgE still remains largely unknown. Here, we discovered that glucocorticoids, which are steroid stress hormones, enhance IgE isotype class switching in B cells both in vivo and ex vivo without antigenic challenge. Such IgE class switching is promoted by B cell-intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, we showed that locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent IgE-mediated pathogenic anaphylaxis in vivo. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.
2022-09-09 | GSE203542 | GEO
Project description:Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by, among others, the excessive production of IgE and repetitive bacterial/fungal infections. Although STAT3 is a known causative factor of HIES, the biological consequences of STAT3 mutation are not completely understood, especially at the epigenetic level. Here, we used multi-omic approaches to decipher the multidimensional immune disturbance in a male HIES patient harboring STAT3-V637M. In his peripheral blood mononuclear cell (PBMC) we found significant clonal expansion of CD8 T cells (whose expression of CD8 subunits was increased, resulting in enhanced responsiveness to MHC I molecules), but not CD4 T cells and B cells in his. The lack of T cells-B cells interaction could be responsible for the limited number of his B cells, although they exhibited a higher potential in producing immunoglobulin, elevated SPIC binding might bias this process toward IgE isotype production. Immune checkpoint inhibitors, including CTLA4, LAG3, were overexpressed in his PBMC-CD4 T cells, accompanied by reduced CD28 and IL6ST (gp130) expression. For his CD4 T cells, integrative analyses predicted upstream transcription factors (ETV6, KLF13, and RORA) for LAG3, IL6ST, and CD28, respectively. The down-regulated phagocytic, and nitric oxide synthetic genes in his PBMC-monocytes seem to be the culprit of his disseminated bacterial/fungal infection. In his bronchoalveolar lavage fluid (BALF), we identified two macrophages with anti-bacterial properties, which were characterized by CXCL8/S100A8/S100A9, or SOD2, respectively. Together, this study comprehensively described how the immune cell landscape was disturbed in STAT3-V637M HIES and provided a resource for further studies on STAT3 biology.
2023-09-07 | GSE212479 | GEO
Project description:Purpose: To identify IgE inhibitory bioactive compound from A.Lappa for targeted therapy on peanut specific IgE production and hypersensitivity reactions, and to investigate its underlying mechanisms. The goals of this study were to compare the transcriptome map (RNA-seq) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) before and after PMBC in patients with food allergy, and to evaluate the most critical genes and signaling pathways which inhibit IgE production by arctigenin.
2022-01-01 | GSE183215 | GEO
Project description:The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE cells in these memory responses is particularly unclear. IgE B-cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B-cell receptor function and increased apoptosis. IgE GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B-cell differentiation fates: direct switching generates IgE GC cells, whereas sequential switching gives rise to IgE plasma cells. We propose a comprehensive model for the generation and memory of IgE responses. The purpose of this analysis was to: 1) identify expression differences between IgE and IgG1 B lymphocytes, 2) identify GC Dark Zone (DZ) and Light Zone (LZ) signatures of IgG1 GC cells. For that purpose, we compared in one experiment the gene expression patterns of IgE germinal center (GC) cells, IgG1 GC cells, IgE plasma cells (PC), IgG1 PC and naïve cells. In a second experiment, we compared the expression of IgG1 DZ GC cells with that of IgG1 LZ GC cells. Triplicates obtained from independent sorting experiments were used for all samples except two (IgG1 PC=2 samples; IgE PC=4 samples). Each sample was obtained from a pool of three individual mice. The mice used in the experiment were CeGFP BALB/c mice infected with the parasite N. brasiliensis. CeGFP mice carry an IRES-GFP KI cassette in the 3'UTR of membrane IgE. In these mice, GFP expression marks IgE cells, and a population of IgG1 cells with a rearrangement to Cepsilon in the non-productive (VDJ negative) IgH chromosome.
2013-10-31 | E-GEOD-49033 | biostudies-arrayexpress
Project description:We report a rare population of IL-13-producing Tfh cells that were present with high-affinity IgE to allergens. These “Tfh13” cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo), co-express BCL6 and GATA3 and were required for production of high- but not low-affinity IgE and accordingly, allergen-induced anaphylaxis.
2019-08-06 | GSE132798 | GEO
Project description:The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE cells in these memory responses is particularly unclear. IgE B-cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B-cell receptor function and increased apoptosis. IgE GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B-cell differentiation fates: direct switching generates IgE GC cells, whereas sequential switching gives rise to IgE plasma cells. We propose a comprehensive model for the generation and memory of IgE responses.
2013-10-31 | GSE49033 | GEO