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Transcriptome analysis of TACI-deficient and WT naïve T cells

ABSTRACT: TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class-switching and plasma cell survival. However, its expression and function in T cells remain controversial. In this study, we found that TACI deficiency in mice results in expansion of TH17 and Treg populations. To understand the mechanisms underlying increased frequencies and numbers of TH17 cells correlated with more severe colitis in TACI-/- mice, microarray-based transcriptome analysis was conducted to identify genes that were differentially expressed in TACI-/- vs WT naive CD4+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE152077 | GEO | 2020/11/23

REPOSITORIES: GEO

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Expression data from Th17 cells of different origins

Project description:Foxp3 is indispensable for Treg suppressive function, but the stability of Foxp3 has been controversial. In autoimmune arthritis, Th17 cells play a critically important pathological role, but the origin of Th17 cells remains unknown We used microarrays to detail the global programme of gene expression of Th17 cells originated from Foxp3+T cells compared to conventional naive CD4+T cells derived Th17 cells. We also take samples of Treg cells and Th0 cells for the experimetnatl control. Each T cell subset after the culture was subjected to RNA extraction and hybridization on Affymetrix microarrays.

2013-12-21 | E-GEOD-48428 | biostudies-arrayexpress

Expression data from Th17 cells of different origins

2013-12-21 | GSE48428 | GEO

Differential pathogenic Th17 profile in mesenteric lymph nodes of Crohn's disease and ulcerative colitis patients

Project description:The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn’s disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6+CXCR3-RORg+Tbet-CD4+ (Th17) memory T cells enriched in CD62Llow effector memory T cells (TEM), and their differentially expressed molecular profile. Th17 TEM cells (expressing IL17A, IL17F, RORC and STAT3) displayed a higher pathogenic/cytotoxic (IL23R, IL18RAP, and GZMB, CD160, PRF1) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (IL9, FOXP3, CTLA4) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNg expression in Th17 TEM and switched their molecular profile towards an ex-Th17 (Th1*)-biased transcriptomic signature (increased IFNG, and decreased TCF7, IL17A), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD.

2019-05-17 | GSE131359 | GEO

Transcriptomic analysis of injured and uninjured knee joints from Trem2 KO mice [bulk RNA-seq]

Project description:Trem2 is a single-pass transmembrane receptor of the immunoglobulin superfamily and is primarily expressed in myeloid cells. Cells from injured and uninjured knee joints of wildtype C57BL/6 mice and Trem2 KO mice were sequenced to determine if Trem2 plays a role in macrophage differentiation or function after joint injury.

2022-07-18 | GSE200842 | GEO

Multi-omics Analysis of naive B cells of patients harboring the C104R mutation in TACI

Project description:Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary immunodeficiency in humans. The genetic cause of CVID is still unknown in about 70% of cases. 10% of CVID patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (TNFRSF13B), encoding TACI. Mutations in TNFRSF13B alone may not be sufficient for the development of CVID, as 1% of the healthy population carry these mutations. The common hypothesis is that TACI mutations are not fully penetrant and additional factors contribute to the development of CVID. To determine these additional factors, we investigated the perturbations of transcription factor (TF) binding and the transcriptome profiles in unstimulated and CD40L/IL21-stimulated naïve B cells from CVID patients harboring the C104R mutation in TNFRSF13B and compared them to their healthy relatives with the same mutation. In addition, the proteome of stimulated naïve B cells was investigated. For functional validation, intracellular protein concentrations were measured by flow cytometry. Our analysis revealed 8% less accessible chromatin in unstimulated naïve B cells and 25 % less accessible chromatin in class-switched memory B cells from affected and unaffected TACI mutation carriers compared to healthy donors. The most enriched TF binding motifs in TACI mutation carriers involved members from the ETS, IRF and NF-B TF families. Validation experiments supported dysregulation of the NF-B and MAPK pathways. In steady state, naïve B cells had increased cell death pathways and reduced cell metabolism pathways; while after stimulation, enhanced immune responses and decreased cell survival was detected. Using a multi-omics approach, our findings provide valuable insights into the impaired biology of naïve B cells from TACI mutation carriers.

2022-10-14 | PXD035459 | Pride

Endogenous B cell TACI-Short-APRIL signaling

Project description:Here we show that TACI-S increases its expression with maturation and colocalizes in the intracellular compartment with the ligand APRIL. APRIL downregulation in human B cells, eliminated class switch. These studies suggest the importance of intracellular APRIL together with TACI-S in maintaining humoral immunity.

2023-09-22 | GSE213981 | GEO

ChIP-seq of H3K18la in murine Th17-differentiated T cells

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2022-11-25 | GSE208727 | GEO

Gene expression profiles from human splenic Marginal Zone and Naive (Follicular) B cells

Project description:Splenic Marginal Zone B cells mount innate-like T cell-independent (TI) antibody responses to blood-borne antigens upon receiving activation signals from TACI-engaging factors BAFF and APRIL. The transcriptome analysis of splenic Marginal Zone (MZ) B cells was performed to verify which transcriptional programs are enhanced in the innate-like MZ B cell subset and to study the involvement of mTOR in MZ B cells activated via TACI.

2017-10-14 | GSE85289 | GEO

Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis

Project description:We correlated comprehensive T cell phenotyping data from peripheral blood to the corresponding genotype of different disease-associated and T cell related SNPs. This revealed significantly increased frequencies of naive CD4+ T cells (CD4+ TN) and T helper 17 (TH17) cells in carriers of intergenic SNP rs56258221 (BACH2/MIR4464) as compared to non-carriers. Functional experiments identified CD4+ TN from SNP-carriers to rather polarize towards pro-inflammatory subsets than into regulatory T cells (TREG). *** Due to data privacy concerns fastq files have not been uploaded ***

2024-04-22 | E-MTAB-14013 | biostudies-arrayexpress

Intergenic risk variant rs56258221 skews the fate of naive CD4+ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis

2024-05-22 | E-MTAB-14103 | biostudies-arrayexpress

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