Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TCR signal strength controls thymic differentiation of discrete proinflammatory γδT cell subsetsistinct TCR signal strength requirements in the thymus

ABSTRACT: The murine thymus produces discrete γδ T cell subsets making either IFN-γ 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 γδ T cells. Mice haploinsufficient for both CD3γ and CD3δ (CD3DH) showed normal αβ thymocyte subsets but specific defects in γδ T cell development, namely impaired differentiation of IL-17-producing embryonic Vγ6+ (but not adult Vγ4+) γδ T cells and a marked depletion of IFN-γ-producing CD122+ NK1.1+ (Vγ1-biased) γδ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-γ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct Vγ usage and differential cytokine production by effector γδ T cell subsets.

ORGANISM(S): Mus musculus

PROVIDER: GSE71637 | GEO | 2016/03/29

SECONDARY ACCESSION(S): PRJNA291693

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

TCR signal strength controls thymic differentiation of discrete proinflammatory Î³Î´T cell subsetsistinct TCR signal strength requirements in the thymus

Project description:The murine thymus produces discrete Î³Î´ T cell subsets making either IFN-Î³ 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 Î³Î´ T cells. Mice haploinsufficient for both CD3Î³ and CD3Î´ (CD3DH) showed normal Î±Î² thymocyte subsets but specific defects in Î³Î´ T cell development, namely impaired differentiation of IL-17-producing embryonic VÎ³6+ (but not adult VÎ³4+) Î³Î´ T cells and a marked depletion of IFN-Î³-producing CD122+ NK1.1+ (VÎ³1-biased) Î³Î´ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-Î³ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct VÎ³ usage and differential cytokine production by effector Î³Î´ T cell subsets. We investigated the transcriptional changes associated with reduced TCRÎ³Î´ signaling in the CD3DH model. Transcriptome-wide analysis of FACS-purified CD3DH or WT Î³Î´ thymocytes from E18 or 6-week was carried looking for patterns of gene expression during ontogeny

2016-03-29 | E-GEOD-71637 | biostudies-arrayexpress

RNA sequencing of gamma-delta T cell subsets from young and old mice

Project description:Organismal ageing is associated with loss of immune function and higher incidence of cancer. Whether the γδ T cell pool changes upon organismal ageing is not known. In this study we have characterized γδ T cells in peripheral lymph nodes from old and young mice. We found that the γδ T cell pool is severely altered in old mice. The IL-17 producing γδ lineage becomes dominating while IFN-γ producing γδ1 T cells are declining. γδTCR sequencing revealed no collapse in diversity but oligoclonal expansions in Vγ4 γδ17 subsets. Pro-tumourigenic invariant Vγ6 cells are present only in aged lymph nodes, represent the majority of γδ T cells in the tumour, and are associated with faster tumour progression.

2019-05-22 | E-MTAB-7178 | biostudies-arrayexpress

Single-Cell RNA Sequencing of Thymic KN6 γδ T-Cells Modulated by TCR Signal Strength and Notch Signaling

Project description:γδ T-cells form an integral arm of the immune system through their rapid and potent effector functions, and are critical players during both protective and destructive immunity. However, the factors that dictate γδ T-cell functional programming in vivo remain to be fully elucidated. Here, we employed RBPJ-inducible and KN6-transgenic mice to assess the roles of ontogenic timing, T-cell receptor (TCR) signal strength, and Notch signaling in the generation of γδ T-cell functional subsets in vivo. We found skewed generation of Vγ1+ cells toward the PLZF+ γδ T-cell lineage at the fetal stage. Similarly, generation of interleukin (IL)-17 producing γδ T-cells was favored during, although not exclusive to, the fetal stage. Strong TCR signals, in conjunction with Notch, were necessary for the generation of IL-4 producing γδ T-cells. Conversely, weak TCR signals were amenable for the generation of IL-17 producing γδ T-cells, which was Notch-independent. Additionally and surprisingly, Notch signaling was also dispensable for peripheral γδ T-cell IL-17 production. Thus, our results precisely defined the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T-cell functional programming in vivo.

2021-05-01 | GSE165908 | GEO

TCR signal strength controls thymic differentiation of iNKT cell subsets

Project description:Three major phenotypically and functionally distinct invariant Natural Killer T (iNKT) cell subsets (iNKT1, iNKT17 and iNKT2), each with propensity to traffic to different tissues and to secrete different cytokines upon activation, have been defined. These fate assignments can be conferred upon iNKT cells during development in the thymus, but the cues that direct these decisions remain unclear. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets in the thymus, with high signaling strength necessary for iNKT2 and iNKT17 development. Alteration of TCR diversity and/or signaling dramatically diminished iNKT2 and iNKT17 cell subset development in a cell intrinsic manner. Decreased TCR signaling affected the persistence of Egr2 expression and the upregulation of PLZF both in vivo and in vitro. Genome-wide chromatin accessibility analysis revealed subset-specific activity of regulatory elements associated with unique signatures of transcription factor binding sites. NFAT and Egr binding motifs were found preferentially enriched in chromatin regulatory regions specifically accessible in iNKT2 cells that were lost in iNKT2 cells that had developed with reduced TCR signaling. Altogether, these data suggest a model of iNKT cell subset development where variable TCR signaling induces changes in chromatin accessibility at NFAT and Egr binding sites which exerts a determinative influence on the dynamic of gene enhancer accessibility that affects the developmental fate of iNKT cells.

2018-05-18 | GSE111427 | GEO

TCR signal strength controls thymic differentiation of iNKT cell subsets

2018-05-17 | GSE110327 | GEO

Vγ6+ γδ T cells play a critical role in protection against infection by Escherichia coli

Project description:γδ T cells producing interleukin 17A (IL-17A), which are mainly Vγ4 and Vγ6 subsets, are involved in protection against infection by extracellular bacteria. Using a new Vγ6-specific monoclonal antibody (mAb) (1C10-1F7) which we recently developed, we found that IL-17A+ Vγ6+ γδ T cells increased predominantly in the peritoneal cavity compared with IL-17A+ Vγ4+ γδ T cells during intraperitoneal Escherichia coli infection. The number of IL-17A+ Vγ6+ γδ T cells, which rapidly became CD69+ from CD69-, peaked at 12 h after infection. In vivo treatment with 1C10-1F7 mAb significantly inhibited the accumulation of neutrophils and hampered the resolution of E. coli infection. These results suggest that rapid activation of IL-17A+ Vγ6+ γδ T cells contributed to host defence against E. coli infection.

2020-02-28 | GSE144617 | GEO

TCR signal strength controls thymic differentiation of iNKT cell subsets

Project description:TCR signal strength controls thymic differentiation of iNKT cell subsets

| PRJNA436981 | ENA

TCR signal strength controls thymic differentiation of iNKT cell subsets

Project description:TCR signal strength controls thymic differentiation of iNKT cell subsets

| PRJNA433481 | ENA

Single cell RNA sequencing of Vγ4 and Vγ6 γδT cells from different tissue

Project description:IL17-producing γδ T cells (γδ 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 Vγ4+ and Vγ6+ TCRs with germline-like rearrangements. In particular, Vγ6+ 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 Vγ6+ T cells isolated from thymus, peripheral lymph nodes (pLN) and skin through single-cell RNA-seq technology and compared those to Vγ4+ T cells. Our data demonstrated that Vγ6+ T cells formed highly homogenous cell populations that could be separated by tissue-specific gene expression signatures.

2018-12-07 | GSE123400 | GEO

γδ-T cells and αβ-TCR transduced γδ-T cells

Project description:RNA expression of unstimulated γδ-T cells,γδ-TCR-stimulated γδ-T cells, unstimulated αβ-TCR transduced γδ-T cells and αβ-TCR-stimulated αβ-TCR transduced γδ-T cells.

2023-09-07 | GSE216880 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data