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SRP061407
Mus musculus
12 Downloadable Samples
Description
GATA3 is indispensable for the development of all IL-7Ra-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Ra expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and ROR?t. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. Overall design: To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.
Publication Title
Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.
Publication Title
Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
In support of our manuscript investigating the roles of ILCs and T cells in the maintenance of gut hoemostasis, we have performed RNAseq on terminal illeum of mice lacking either all adaptive immune cells (RAG1 -/-), deficient in T cells (TCRalpha -/-), or deficient in T cells but co-housed with wild-type mice and RAG1 -/- mice. Overall design: Tissues from three mice per group were analysed, and the following comparisions were made: RAG1-/- vs. WT C57BL/6 and TCRa-/- co-housed vs TCRa-/- seperately housed. Differential expression genes were identified at 1% FDR using DESeq2.
Publication Title
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
T cell-specific transgenic expression of microRNA-181d reduced number of immature CD4+CD8+ thymocytes.
Publication Title
Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+)CD8(+) thymocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung, but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4+-regulatory T (Treg) cell induction, and restrain CD8+ T cell effector function. Tumor colonization is accompanied by PHD protein-dependent induction of pulmonary Treg cells and suppression of IFN-g-dependent tumor clearance. T cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis. Overall design: RNA expression was measured by RNA-Seq at day 4 following stimulation of naïve FACS-sorted CD4+ T cells with anti-CD3 and anti-CD28 antibodies in the presence of indicated doses of TGF-b. Gene expression was analysed separately in control Cd4Cre (WT) and Egln1fl/fl Egln2fl/fl Egln3fl/fl Cd4Cre (tKO) cells, or in cells treated with the pharmacological PHD inhibitor dimethyloxaloylglycine (DMOG) and control vehicle-treated cells.
Publication Title
Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
In this experiment we profiled the transcriptome of intestinal colonic epithelium and total colonic tissue of animals colonized with T.mu versus naïve littermate controls at different time points Overall design: Groups of three mice were inoculated with 2x106 highly purified Tritrichomonas musculis. Total tissue and epithelial cells were collected at 3 days, 14 days and 48 days after inoculation from three different mice. RNA was isolated and sequenced
Publication Title
Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
IL-23 negatively regulates St2 and Gata3 expression in intestinal CD4+ T cells
Publication Title
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment, and deficient production of reactive oxygen species and cytotoxicity following chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.
Publication Title
Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Publication Title
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples