Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tissue-specific interferon-gamma levels drive regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer

ABSTRACT: Regulatory T cells (Tregs) are proposed to restrain anti-tumor T cell responses either directly or by suppression of antigen-presenting cells and can act in a tissue-specific manner. Treg abundance is typically reported as a measure of suppression, without consideration of Treg functional quality. Here, we find that Tregs suppress type 1 conventional dendritic cells (DC1) and thereby induce dysfunctional CD8+ T cell responses against lung cancer. This immunoregulatory effect is spatially coordinated within tissue-specific lymph node microniches and requires antigen-specific contact between DC1 and Tregs. Suppressive clonally expanded TH1-like effector Tregs were differentially induced in the lung lymph node in response to tissue-specific levels of interferon-gamma. In cancer patients, TH1-like Tregs but not CD8+/Treg ratios correlate with poor responses to checkpoint blockade immunotherapy. Thus, Tregs that adopt the interferon-gamma-dependent TH1-like effector state have increased potential to restrain tumor-reactive T cell responses and represent a critical barrier to productive anti-tumor immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE216086 | GEO | 2022/11/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

TIGIT+ Tregs

Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses. TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes) TIGIT: T cell immunoreceptor with Ig and ITIM domains

2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress

CXCR3+ Treg cells suppress Th1-immune responses through expression of the co-inhibitory receptors CD85k and Lag-3

Project description:CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Tregs to the site of inflammation, however, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated models. Our analysis defined a set of Th1-specific co-inhibitory receptors that are specifically expressed in Treg cells during Th1 immune responses. Among these, we identified the novel co-inhibitory receptor CD85k as a functional mediator of the enhanced suppression of Th1 effector cells by CXCR3+ Treg cells.

2018-06-30 | E-MTAB-6156 | biostudies-arrayexpress

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

Project description:Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

2020-05-26 | E-MTAB-9112 | biostudies-arrayexpress

TIGIT+ Tregs

2014-12-12 | GSE56299 | GEO

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

Project description:Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

2020-05-22 | GSE115545 | GEO

Myocardial infarction (MI) primes autoreactive T cells through activation of dendritic cells

Project description:DC subsets of the murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2 and monocyte-derived DCs. In steady state, cardiac self-antigen α-myosin was presented in heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4+ TCR-M T cells, and their differentiation into Tregs. Following MI, all DC subsets infiltrated the heart, while only cDCs migrated to the mLN. Here, cDC2s induced TCR-M proliferation and differentiation into IL-17/IFNγ producing effector cells. Thus, cardiac specific autoreactive T cells get activated by mature DCs following myocardial infarction.

2017-03-15 | GSE94949 | GEO

Gene expression of murine iDCs isolated from tolerized MOG35-55-infused/MOG35-55-immunized or MOG35-55-immunized mice

Project description:Recent data from our group, demonstrate that infusion of myelin oligodendrocyte glycoprotein (MOG35-55) peptide, leads to induction of MOG35-55-specific Tregs and subsequent suppression of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis. Amelioration of EAE was accompanied by reduced MOG-specific Th1 and Th17 responses in the draining lymph nodes (dLNs). Phenotypic analysis of the dLNs of MOG-infused mice revealed a significant Treg-mediated reduction in the recruitment of 7AAD-CD3-CD19-CD11c+CD11bhighGr-1+ iDCs compared to non-infused control immunized mice. Focusing on the delineation of novel molecules/genes that are involved in the MOG-specific Treg-mediated suppression of autoimmune responses, we have isolated highly purified iDCs from MOG infused and non-infused control immunized mice.

2015-04-20 | GSE47210 | GEO

MicroRNA profiling of mouse T regulatory cells (Tregs) reveals miRNA disruption in Tregs leads to uncontrolled autoimmunity

Project description:A new Treg-specific, FoxP3-GFP-hCre BAC transgenic was crossed to a conditional Dicer knock-out mouse strain to analyze the role of microRNAs (miRNA) in the development and function of regulatory T cells (Tregs). Although thymic Tregs developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient Treg lineage cells failed to remain stable as a subset of cells down-regulated the Treg-specific transcription factor, FoxP3, while the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, GITR and CTLA-4) associated with the Treg fingerprint. In fact, a significant percentage of the Treg lineage cells took on a Th memory phenotype including increased levels of CD127, IL-4, and interferon-g. Importantly, Dicer-deficient Tregs lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 knockout phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated Treg function in vivo and homeostasis of the adaptive immune system. Experiment Overall Design: Lymph node CD4+YFP+ T cells from FoxP3-GFP-hCre x ROSA26R-YFP Dicerwt/lox (Het) and FoxP3-GFP-hCre x ROSA26R-YFP Dicerlox/lox (KO) mice were isolated by flow cytometry. Triplicate GeneChips were used for each T cell population.

2008-10-21 | E-GEOD-11818 | biostudies-arrayexpress

Targeted next generation sequencing of 589 genes identifies complementary responses in t-helper-like T regulatory cells

Project description:Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral immunological tolerance, by preventing autoimmunity and chronic inflammation. However, they can also play a parallel role in the promotion of antitumor responses. Tregs can be classified as T helper (Th)-like Tregs that phenotypically resemble Th1/Th2/Th17/TH1-TH17 lineages based upon the expression of specific chemokine receptors and transcription factors. The distribution of these Treg subsets can provide mechanistic insights into disease processes, therefore we sought to characterise their immune transcriptome. Targeted RNA sequencing revealed that circulating Th2-like Tregs displayed higher viability and activation as well as suggesting specific disease pathways associated to sifferent T reg subtypes.

2017-06-12 | GSE99733 | GEO

Transcription Profiles of Regulatory T Cells in Follicular Lymphoma Lymph Nodes, Normal Lymph Nodes and Reactive Lymph Nodes

Project description:We have previously shown that Tregs infiltrating follicular lymphoma lymph nodes (FLN) are quantitatively and qualitatively different than those infiltrating normal and reactive nodes (NLN, RLN, respectively). To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of FLN tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of CXCR5, CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how FLN Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.

2016-05-26 | GSE74102 | 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