Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Progressively Differentiated Tfh13 Cells are Stabilized by JunB to Mediate Allergen Germinal Center Responses

ABSTRACT: Allergic diseases are common and affect a large proportion of the population. IL-13-expressing follicular T (Tfh13) cells are a newly identified population of Tfh cells that have been associated with high affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of Tfh13 cells are unknown. Here, we examined the developmental signals for Tfh13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar Tfh13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based Tfh13-DTR model to perturb these cells, we found that Tfh13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by Tfh13 cells to amplify allergic responses. Thus, Tfh13 cells orchestrate multiple features of allergic inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE279058 | GEO | 2024/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Type 2-polarized memory B cells hold allergen-specific IgE memory

Project description:Allergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rαhi, CD32low at the transcriptional and surface protein levels.

2023-11-25 | GSE248256 | GEO

T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

Project description:Immunoglobulin E (IgE) is a potent mediator of allergic diseases, but the mechanisms that regulate IgE responses to innocuous environmental and food antigens remain unclear. Patients with Loeys-Dietz syndrome (LDS) who have mutations in genes encoding the TGFβ receptor are predisposed to IgE-mediated disorders. Here, using patient samples and a mouse model, we demonstrate that LDS mutations lead to reduced canonical TGFβ signaling, elevated total and allergen-specific IgE, increased type 2 follicular helper T cells (Tfh2), and exaggerated germinal center activity that was not prevented by the presence of wild type T regulatory cells. T cell intrinsic defects in LDS mice resulted in spontaneous sensitization to orally administered OVA, and inhibition of mammalian target of rapamycin (mTOR) prevented the exaggerated Tfh and IgE responses to OVA. Thus, TGFβ limits human and mouse Tfh2 cell development via the phosphatidylinositol-3-OH kinase gamma (PI3Kg)/AKT/mTOR pathway, and disruption of this pathway promotes allergic inflammation.

2023-08-01 | GSE202688 | GEO

T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

2023-08-01 | GSE203379 | GEO

Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory

Project description:Summary: Long-lived IgE plasma cells reside in the bone marrow of allergic mice and atopic humans, confer IgE serological memory and produce allergen-specific IgE that can drive anaphylaxis. Abstract: Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We re-examined the mechanism of serological memory in allergy using a dual-reporter system to track IgE plasma cells (PCs) in mice. Short-term allergen exposure resulted in the generation of IgE plasma cells that resided mainly in secondarylymphoid organs and produced IgE that was unable to degranulate mast cells. In contrast, chronic allergen exposure led to the generation of long-lived IgE plasma cells that were primarily derived from sequential class switching of IgG1, accumulated in the bone marrow (BM) and produced IgE capable of inducing anaphylaxis. Most importantly, IgE plasma cells were found in the BM of human allergic, but not non-allergic donors, and allergen-specific IgE produced by these cells was able to induce mast cell degranulation when transferred to mice. These data demonstrate that longlived IgE BMPCs arise during chronic allergen exposure and establish serological memory in both mice and humans.

2019-11-16 | GSE140435 | GEO

scRNA-seq of day 32 p.i. GC B cells induced by experimental Plasmodium infection following the inducible deletion of IL-21 from CD4 T cells on day 16-18

Project description:IL-21 is critical for initiating humoral immune responses, but whether sustained IL-21 production by T follicular helper cells regulates the quality or output of memory B cells and plasma cells during an established germinal center response is unknown. Here, we applied scRNA and approaches to determine the heterogeneity of germinal center B cells from Plasmodium infected mice with or without truncated IL-21 expression.

2024-04-24 | GSE253397 | GEO

Identification of a T follicular helper subset that drives anaphylactic IgE

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

Transcriptome analysis of mouse IgG1 memory B cell subsets

Project description:IgE plays an essential role in the pathogenesis of allergies and its production is strongly regulated. A transient IgE germinal center phase and lack of IgE memory cells limit the generation of pathogenic IgE, but this can be overcome by sequential switching of IgG1 cells to IgE. We investigated which population of IgG1 cells can give rise to IgE-producing cells in memory responses. We identified three populations of IgG1 memory B cells (DP:CD73+CD80+, SP:CD73-CD80+, DN:CD73-CD80-) that generate IgE plasma cells of high or low affinity, but none gives rise to IgE germinal center cells or IgE memory cells. The two memory IgG1 populations differ however in their ability to differentiate into IgG1 plasma cells and germinal center cells, and to expand the IgG1 memory B cell pool. To explore the molecular mechanisms that may explain the distinct functions of IgG1 memory B cell subsets we compared their expression by transcriptome analysis using next generation sequencing.

2017-07-03 | GSE83436 | GEO

IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

Project description:Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE. However, the underlying mechanism by which IL-6 may prevent the development of Th2-driven diseases remains unknown. Using a model of house-dust-mite (HDM)-induced Th2 differentiation and allergic airway inflammation, we show here that IL-6 signaling in allergen-specific T cells was required to prevent Th2 development and subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. Importantly, we found that IL-6 turned off IL-2 signaling during early T cell activation and thus inhibited Th2 cell priming. Mechanistically, we found that IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of suppressor of cytokine signaling 3 (SOCS3). Therapeutically, this mechanism can be mimicked by JAK1 inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

2023-04-07 | GSE212158 | GEO

Origins and diversity of pan-isotype human bone marrow plasma cells

Project description:Bone marrow plasma cells (BMPCs) produce durable, infection-resistant IgM, IgG, and IgA antibodies, but in some cases, pro-allergic IgE. Despite this, BMPC sources are unclear. We charted single BMPC transcriptional and clonal heterogeneity in peanut-allergic and non-allergic humans across CD19 protein expression—due to CD19’s inverse correlation to BMPC longevity. Transcriptional and clonal diversity revealed distinct functional modules. Additionally, distributions of somatic hypermutation and intraclonal antibody sequence variance suggest CD19low and CD19high BMPCs arise from recalled memory and germinal center B cells, respectively. Most IgE BMPCs were from peanut-allergic individuals; some bound peanut and potently prevented peanut-driven anaphylaxis in a mouse model. These findings shed light on BMPC origins and identify the bone marrow as a likely source for long-lived pathogenic IgE in peanut allergy.

2024-05-01 | GSE262896 | GEO

Effect of Intradermal Immunotherapy (IDIT) injections on gene expression profiles of activated T cells derived from skin biopsy explants

Project description:A Randomized, Placebo-Controlled Trial of Intradermal Allergen Immunotherapy for Grass Pollen Allergy Background: Repeated intradermal injection of grass pollen (nanograms of allergen) suppresses allergen-induced cutaneous late phase responses, in keeping with effects of conventional high dose subcutaneous and sublingual immunotherapy. We evaluated the efficacy and safety of grass pollen intradermal immunotherapy for treatment of allergic rhinitis.Methods: We randomly assigned 93 adults with grass pollen allergic rhinitis to receive 7 pre-seasonal Intradermal allergen immunotherapy injections (containing 7 ng of Phl p 5 major allergen) or histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season. Skin biopsies were taken after the pollen season following an intradermal allergen challenge. Cutaneous late phase responses were measured 4 and either 7, 10 or 13 months post-treatment. Results No difference in the primary endpoint was observed between treatment arms (median difference, 14; 95% confidence interval [CI], -172.5 to 215.1; P=0.80). Amongst secondary endpoints, nasal symptoms measured with daily scores (median difference, 35; 95% CI, 4.0 to 67.5; P=0.03) and visual-analogue scales (median difference, 53; 95% CI, -11.6 to 125.2; P=0.05) were higher in the intradermal treatment group. Intradermal immunotherapy increased serum Phl p-specific IgE (P=0.001) compared to the control arm and T cells cultured from biopsies showed higher and lower surface of surface markers for Type 2 (P=0.04) and Type 1 (P=0.01) T-helper cells, respectively, Interleukin-5 was differentially expressed by microarray (P=0.03). Late phase responses were still inhibited 7 months after treatment (P=0.03) but not at 10-13 months. Conclusions Grass pollen intradermal allergen immunotherapy was not clinically effective but resulted in immunological priming and worsening of allergic rhinitis symptoms.

2017-06-23 | GSE72324 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data