Secretory IgA binding to FCRL3 triggers shared inflammatory cytokine secretion by human regulatory T cells and effector T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1160252 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30646000_1.fastq.gz | Fastqsanger.gz | |||
| SRR30646000_2.fastq.gz | Fastqsanger.gz | |||
| SRR30646100_1.fastq.gz | Fastqsanger.gz | |||
| SRR30646100_2.fastq.gz | Fastqsanger.gz | |||
| SRR30646001_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 288 |
Similar Datasets
Project description:Several human lymphocyte subsets express the novel secretory IgA receptor FCRL3. Secretory IgA binding to FCRL3 mAb diminishes the inhibitory capacity of regulatory T cells and promotes a Th17-like phenotype. Here we report that in CD4+ regulatory T cells and CD8+ terminal effector T cells secretory IgA induced a shared inflammatory gene signature that included PTGS2 encoding COX2, and the prototypic inflammatory cytokine genes IL1A, IL1B, and IL8. Secretory IgA in regulatory T cells also elevated gene transcripts required for lineage identity and function. Secretory IgA promoted IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α protein secretion by both T cell types. . We propose that secretory IgA provokes in regulatory and effector T cells a coordinated inflammatory response to facilitate mucosal pathogen clearance.
2025-04-07 | GSE277028 | GEO
Project description:Fusobacterium nucleatum (Fn), enriched in human colorectal cancer (CRC), is linked to a worse prognosis. To uncover the cellular and molecular mechanisms behind this Fn-associated prognostic effect, we conducted single-cell transcriptomic analyses on 42 surgically removed colon tissues from newly diagnosed colon cancer patients. Through single-cell and spatial transcriptome data analyses, we found that the development of IgA plasma cells producing functional secretory IgA was impaired due to disrupted communications between IgA plasma cells and macrophages in Fn-positive CRC. Additionally, we identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised IgA-mediated mucosal immunity. This finding was further supported by observed increases in bacterial infiltration within tumors of Fn-positive patients. Remarkably, we were able to stratify Fn-positive patients based on IGAM activity, which could lead to novel treatment strategies for Fn-positive CRC patients. Our findings indicate that impaired secretory IgA activity by Fn infection increases the bacterial burden within tumors and worsens prognosis through chronic inflammation. Additionally, identifying a novel gene expression biomarker for stratifying Fn-positive patients promises to refine CRC treatment strategies, offering a more tailored approach to patient care.
2025-07-23 | GSE273567 | GEO
Project description:Fusobacterium nucleatum (Fn), enriched in human colorectal cancer (CRC), is linked to a worse prognosis. To uncover the cellular and molecular mechanisms behind this Fn-associated prognostic effect, we conducted single-cell transcriptomic analyses on 42 surgically removed colon tissues from newly diagnosed colon cancer patients. Through single-cell and spatial transcriptome data analyses, we found that the development of IgA plasma cells producing functional secretory IgA was impaired due to disrupted communications between IgA plasma cells and macrophages in Fn-positive CRC. Additionally, we identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised IgA-mediated mucosal immunity. This finding was further supported by observed increases in bacterial infiltration within tumors of Fn-positive patients. Remarkably, we were able to stratify Fn-positive patients based on IGAM activity, which could lead to novel treatment strategies for Fn-positive CRC patients. Our findings indicate that impaired secretory IgA activity by Fn infection increases the bacterial burden within tumors and worsens prognosis through chronic inflammation. Additionally, identifying a novel gene expression biomarker for stratifying Fn-positive patients promises to refine CRC treatment strategies, offering a more tailored approach to patient care.
2025-07-23 | GSE288951 | GEO
Project description:Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis
| PRJNA840855 | ENA
Project description:Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated protein Plekhg5 drives the UPS of Sod1. Mechanistically, Sod1 is sequestered into the intermembrane space of autophagosomes which fuse with secretory lysosomal-related organelles (LROs). Deletion of Plekhg5 in mice disrupts the secretion of these LROs causing Sod1 accumulation at swollen presynaptic sites. A reduced secretion of toxic ALS-linked SOD1G93A following deletion of Plekhg5 in SOD1G93A mice accelerated disease onset while prolonging survival due to an attenuated microglia activation. Using human isogenic iPSC-derived motoneurons we show an impaired secretion of ALS-linked SOD1D90A, which coincided with a reduced PLEKHG5 expression. Our findings highlight an unexpected pathophysiological mechanism that converges two motoneuron disease-associated proteins into a common pathway.
2024-08-28 | GSE269588 | GEO
Project description:MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells shows that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidycitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T cells; however, the role of PADs in B cells remains to be elucidated. In an unbiased analysis of the human citrullinomeic analysis, we found that MZB1 was preferentially enriched in the pool of citrullinated lung proteins obtained from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) compared to those from idiopathic pulmonary fibrosis or chronic obstructive pulmonary diseases. The citrullination of MZB1 was confirmed with mass spectrometry, in vitro citrullination, and binding by phenylglyoxal in the absence or presence of a PAD2-specific inhibitor AFM-30a. Ablation or pharmacological inhibition of PAD2 in primary human B cells attenuated the secretion of IgM and IgA but not IgG or the differentiation of IgM or IgA-expressing plasmablasts, recapitulating the effect of ablating MZB1. In addition, the physical interaction between endogenous MZB1 and IgM/IgA was attenuated by AFM-30a. Taken together, our data confirm the function of MZB1 in primary human plasmablasts and suggest that PAD2 promotes IgM/IgA secretion by citrullinating MZB1, thereby contributing to the pathogenesis of rheumatoid arthritis and RA-ILD.
2023-11-23 | PXD047044 | Pride
Project description:Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer
| PRJNA1142424 | ENA
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
Project description:Plekhg5 regulates the unconventional secretion of Sod1 by presynaptic secretory autophagy
| PRJNA1122581 | ENA
Project description:Despite their long half-life, therapeutic antibodies are considered ineffective against intracellular antigens due to their perceived inability to penetrate epithelial cells. Using recombinant antibodies targeting common mutations in oncogenes, we show that dimeric IgA, but not the same antibody on an IgG backbone, penetrates human epithelial cancer cells through PIGR-dependent directional transcytosis, specifically neutralizing mutated oncodrivers and expelling antigens outside the cell, bound to secretory IgA. Accordingly, targeting of KRasG12D or IDH1R132H with antigen-specific dimeric IgA abrogated the growth of different carcinomas in a mutation-specific manner, including in syngeneic tumor-bearing immunocompetent mice. Our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target common mutations in intracellular oncogenes that drive many aggressive and frequent human cancers.
2025-05-06 | PXD042914 | Pride