Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinct metabolic programs control the effector fate of γδ T cell subsets and their activities in the tumour microenvironment

ABSTRACT: Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here we found that γδ T cell subsets making either IFN-γ or IL-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during γδ thymic development, and were stably maintained in the periphery and within tumours.

ORGANISM(S): Mus musculus

PROVIDER: GSE150585 | GEO | 2020/09/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Meningeal γδ T cells producing IL-17 control synaptic plasticity and cognitive behaviour

Project description:The conventional notion of “immune privilege” of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology (Louveau, Trends Immunol 2015; Kipnis science 2016; Filiano, Nat Rev Neurosciences 2017). Surprisingly, such neuroimmune functions have been linked to “pro-inflammatory” cytokines like IL-4 or IFN-α, shown to control behavioural and social cognition (Derecki, JEM 2010; Filiano, Nature 2016). Here we identify a pro-cognitive role for IL-17 in short-term memory that derives from a previously unknown meningeal-resident γδ T cell subset. This was mostly composed of foetal thymic-derived Vγ6+ T cells, found in the meninges at birth and persisting throughout life, where they were strikingly polarized towards IL-17 production. In fact, γδ T cells were the overwhelming source of meningeal IL-17, whereas IFN-γ was mostly provided by T cells. To assess whether the constitutive production of IL-17 by γδ T cells influenced the cognitive performance of mice, we tested TCRδ-/-, IL-17-/- and respective WT littermate control mice in classical learning paradigms. We observed that mice deficient either for γδ T cells or IL-17 displayed impaired short-term memory in the Y maze paradigm, while retaining normal long-term spatial memory in the Morris water maze. A detailed proteomics analysis of the hippocampus provided mechanistic insight into reduced plasticity of the glutamatergic synapses in the absence of IL-17, which associated with impaired Long Term Potentiation (LTP). Conversely, IL-17 enhanced glial cell production of Brain Derived Neurotropic Factor (BDNF), whose exogenous provision rescued the LTP defect of IL-17-/- animals. Altogether, our data demonstrate that foetal-derived γδ T cells populate the brain meninges where they regulate synaptic plasticity and short-term memory through a non-inflammatory IL-17-dependent mechanism.

2019-10-16 | PXD007574 | Pride

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

Project description: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.

2016-03-29 | GSE71637 | GEO

Multimodal profiling reveals site-specific adaptation and tissue residency hallmarks of γδ T cells across organs in mice

Project description:γδ T cells perform heterogeneous functions in homeostasis and disease across tissues. However, it is unclear whether these roles correspond to distinct γδ subsets or to a homogeneous population of cells exerting context-dependent functions. Here, by cross-organ multimodal single-cell profiling, we reveal that various mouse tissues harbor unique site-adapted γδ subsets. Epidermal and intestinal intraepithelial γδ T cells are transcriptionally homogeneous and exhibit epigenetic hallmarks of functional diversity. Through parabiosis experiments, we uncovered cellular states associated with cytotoxicity, innate-like rapid IFN-γ production and tissue repair functions displaying tissue residency hallmarks. Notably, our observations nuance the link between IL-17-producing γδ T cells and tissue residency. Moreover, transcriptional programs associated with tissue-resident γδ T cells are analogous to those of CD8+ tissue-resident memory T cells. Altogether, this study provides the first multimodal landscape of tissue-adapted γδ T cells, revealing heterogeneity, lineage relationships and their tissue residency program.

2023-11-05 | GSE222454 | GEO

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

Transcriptional signature of human pro-inflammatory TH17 cells [ex vivo TH17 cells]

Project description:Human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ–IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have similar gene signatures to mouse pathogenic TH17 cells.

2017-09-29 | GSE104021 | GEO

RNA Sequencing of Fetal and Adult Mature Thymic Vγ1+ γδ T-Cells

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 | GSE166086 | GEO

γδ T cells orchestrate the induction of protective type 2 immunity in neonatal influenza infection

Project description:Influenza infection causes high rates of hospitalization and mortality in infants. γδ T cells are critical for immune responses against pathogens as regulators and effectors, especially in infants, and yet the roles of neonatal γδ T cells in influenza remain to be investigated. Here we report that γδ T cells were protective against mortality associated with neonatal influenza infection. Infection induced the accumulation and activation of γδ T cells, which transiently expressed IL-17a to enhance early IL-33 production by lung epithelial cells via STAT3 phosphorylation. Subsequently, this led to type 2 immune responses with elicited infiltration of ILC2s and Tregs resulting in increased amphiregulin secretion and tissue repair. Loss of γδ T cells did not alter viral clearance or IFN-γ production. Thus, our results identify a specific requirement for γδ T cells in influenza-infected neonates by initiating type 2 immune responses, mediating tissue homeostasis, and promoting lung integrity.

2018-06-20 | GSE99683 | GEO

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

2021-05-01 | GSE165908 | GEO

Breast cancer stem cell-derived tumors escape from γδ T cell immunosurveillance in vivo by modulating γδ T cell ligands

Project description:Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.

2023-07-20 | PXD039463 | Pride

RORγt inhibition selectively targets IL-17 producing human iNKT and γδ-T cells enriched in Spondyloarthritis while preserving IL-22 responses

Project description:Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but how they contribute to disorders such as SpA is still unclear. Here we describe the presence of particular RORγt+T-betloPLZF- iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt+ iNKT and γδ-hi T cells showed profound IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed a unique Th17 skewed phenotype and gene expression profile. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, these findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.

2018-11-17 | GSE122624 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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