The murine thymus produces discrete T cell subsets making either IFN- or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on T cells. Mice haploinsufficient for both CD3 and CD3 (CD3DH) showed normal thymocyte subsets but specific defects in T cell development, namely impaired differentiation of IL-17-producing embryonic V6+ (but not adult V4+) T cells and a marked depletion of IFN--producing CD122+ NK1.1+ (V1-biased) T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN- responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct V usage and differential cytokine production by effector T cell subsets.
TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
Specimen part
View SamplesIL17-producing ?d T cells (?d T17) mainly develop in the prenatal phase and persist as long-living self-renewing effector cell in all kind of tissues. They express polyclonal T-cell receptors (TCR), comprising public V?4+ and V?6+ TCRs with germline-like rearrangements. In particular, V?6+ T cells have recently been found in a variety of tissues including enthesis, gingiva or skin. However, their exchange between tissues and the mechanisms of tissue-specific adaptation and residency remain poorly understood. Here, we profiled V?6+ T cells isolated from thymus, peripheral lymph nodes (pLN) and skin through single-cell RNA-seq technology and compared those to V?4+ T cells. Our data demonstrated that V?6+ T cells formed highly homogenous cell populations that could be separated by tissue-specific gene expression signatures. Overall design: Sort V?4 and V?6 ?dT cells from peripheral lymph nodes, ear skin and thymus, then do 3'-RNA single cell sequencing (10x genomics).
Single-Cell Transcriptomics Identifies the Adaptation of Scart1<sup>+</sup> Vγ6<sup>+</sup> T Cells to Skin Residency as Activated Effector Cells.
Age, Specimen part, Cell line, Subject
View SamplesWe comprehensively explored Fas expression (protein and mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, using flow cytometry, [3H]-thymidine incorporation and microarray analysis in PBMC from HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients.
A Fas<sup>hi</sup> Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.
Specimen part, Disease stage, Treatment
View SamplesAn efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Specimen part
View SamplesRNAseq analysis of BAFF in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in BAFF-stimulated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with BAFF. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Specimen part, Treatment, Subject
View SamplesRNAseq analysis of CD40 in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Specimen part, Treatment, Subject
View SamplesRNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Age, Specimen part, Subject
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relafl/flCD19-Cre (furtheron designated as RELA) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor RELA in activated B cells. Overall design: Splenic B cells from 12-week old relafl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relfl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor c-REL in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (24 hours) murine relfl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor c-REL in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 24 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View Samples