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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq03, bulk-RNAseq)

ABSTRACT: Different numbers of naive murine CD4+ T cells were cultured at different seeding cell densities and under different polarizing conditions in 96-well plates coated with anti-CD3/anti-CD28 for 3.5 days in the presence of 2 or 5 ng/ml TGF-β (Tfh2 or Tfh5) or with anti-TGF-β (TfhA), sorted by flow cytometry, and subjected to bulk RNA-seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE197425 | GEO | 2024/03/01

REPOSITORIES: GEO

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq02, bulk-RNAseq)

Project description:Naive murine CD4+ T cells from GREAT/SMART-17A mice were cultured under Th1 or Tfh(1 ng/ml TGF-β)-polarizing conditions in 96-well plates coated with anti-CD3/anti-CD28 for 3.5 days; sorted by flow cytometry on IFNg+ (Th1), or CXCR5-IL17A+ (Th17) and CXCR5+IL17A- (Tfh); and subjected to bulk RNA-seq.

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq01, bulk-RNAseq)

Project description:Naive murine CD4+ T cells were cultured under different polarizing conditions in 96-well plates coated with anti-CD3/anti-CD28 for 3.5 days, sorted by flow cytometry, and subjected to bulk RNA-seq.

2024-03-01 | GSE198370 | GEO

TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq04, scRNA-seq)

Project description:Naive murine CD4+ T cells were cultured under different polarizing conditions in 96-well plates coated with anti-CD3/anti-CD28 for 0, 0.5, 1.5, 3.5 days, sorted by flow cytometry, and subjected to single-cell RNA-seq.

2024-03-01 | GSE197842 | GEO

TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq02, bulk-RNAseq)

Project description:TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq02, bulk-RNAseq)

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq01, bulk-RNAseq)

Project description:TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq01, bulk-RNAseq)

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq04, scRNA-seq)

Project description:TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq04, scRNA-seq)

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq05, bulk-RNAseq)

Project description:TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq05, bulk-RNAseq)

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TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq03, bulk-RNAseq)

Project description:TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf (Seq03, bulk-RNAseq)

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Pro-tumor Tfh2 cells induce detrimental IgG4 production and PGE2-dependent IgE inhibition in pancreatic cancer (tfh)

Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is characterized by predominant pro-tumor Th2-type inflammation. T follicular helper (Tfh) cells are relevant immunoregulators in cancer, and often correlate with better survival. How the Th2-skewed microenvironment in PDAC modulates the differentiation of Tfh cells and their immunoregulatory function is unknown. Methods: We carried out high-dimensional flow cytometry and T-cell receptor- and RNA-sequencing, as well as bioinformatics, immunohistochemistry and in vitro mechanistic studies. Findings: We identified Tfh1-, Tfh2-, and Tfh17-like cell clusters in the blood, tumors and tumor draining lymph-nodes (TDLNs) of chemo-naïve PDAC patients and showed that high percentages of Tfh2 cells within the tumor tissue and TDLNs correlated with reduced patient survival. Moreover, only Tfh2 cells were highly activated and were reduced in frequency in patients who responded to neoadjuvant chemotherapy. RNA-sequencing analysis of immunoglobulin expression showed that tumor and TDLN samples expressed all immunoglobulin (IGH) isotypes apart from IGHE. Consistent with these findings, Tfh2 cells differentiated in vitro by tumor microenvironment-conditioned dendritic cells promoted the production of anti-inflammatory IgG4 antibodies by co-cultured B cells, dependent on IL-13. Moreover, unexpectedly, Tfh2 cells inhibited the secretion of pro-inflammatory IgE, dependent on prostaglandin E2. Interpretation: Our results indicate that in PDAC, highly activated pro-tumor Tfh2 favor anti-inflammatory IgG4 production, while inhibit pro-inflammatory IgE. Thus, targeting the circuits that drive Tfh2 cells, in combination with chemotherapy, may re-establish beneficial anti-tumor Tfh–B cell interactions and facilitate more effective treatment.

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Project description:We have shown that TGFb in combination with IL-6 potently induces a T follicular helper cell (Tfh) cell phenotype in activated murine CD4+ T cells in vitro. The transcription factor c-Maf critically contributes to the differentiation of Tfh cells in vitro and in vivo.

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