Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The chemokine receptor CXCR3 promotes CD8+ T cell dependent lung pathology during influenza pathogenesis

ABSTRACT: Purpose: A growing body of evidence highlights the association of exuberant CD8+ T cell responses with influenza acute lung injury. Given their indispensable role in viral clearance, we studied the double-edged function of CD8+ T cells as a bridge between infection resolution and lung pathology. Methods: we performed scRNA-Seq to study the cellular heterogeneity and regulation of cellular response in CD8+ T cells during peak viral (day 7) and post-viral resolution phase (day 14). Results: Our single-cell RNA-Seq data reveal significant differences in CD8+ T cell heterogeneity during different stages of influenza infection (peak viral load vs. infection resolved state). While CXCR3hi CD8+ T effector memory (Tem) was associated with a more robust cytotoxic response (compared to CXCR3low CD8+ T central memory, Tcm), both CD8+ Tem and Tcm exhibited equally potent effector function. The ablation of CXCR3 mitigates lung injury without affecting viral clearance. IFN-gamma was dispensable to the recruitment and regulation of cytotoxic response of CXCR3+ CD8+ T cells. Using scRNAseq, we identified unique regulons associated with regulating cytotoxic response in CXCR3hi CD8+ T cells. Conclusions: Collectively, our data identify CXCR3 as a potential therapeutic target to curb lung injury during influenza pathogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE186839 | GEO | 2021/10/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cross-presenting CD103+ dendritic cells are protected from influenza virus infection

Project description:CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of cross-presentation to the induction of anti-viral cytotoxic T cells remains debated. Here, we used a recombinant influenza virus expressing a NS1-GFP reporter gene to visualize the route of antigen presentation by lung dendritic cells (DC) upon viral infection in vivo. We found that lung CD103+ DC are the only subset to carry intact GFP protein to the draining lymph nodes. Strikingly, lung migratory CD103+ DC are not productively infected by influenza virus and thus induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also show that CD103+ DC resistance to infection correlates with an increased antiviral state in these cells that is dependent on the expression of IFN receptor alpha. In conclusion, these results establish that efficient cross-priming by migratory lung DC is coupled to the acquisition of an anti-viral status, which is dependent on type I IFN signaling pathway. mRNA profiles were generated by deep-sequencing in Illumina HiSeq2000 from alveolar macrophages and CD103+ dendritic cells from lungs of untreated and flu-treated mice

2013-06-19 | E-GEOD-38838 | biostudies-arrayexpress

Gene expression differences between low IL2/7- and high IL-2-expanded CD8+ T effectors at day 8 of LCMV Armtrong infection

Project description:Here, we reported a novel subset of CD8+ T effectors with transcriptional similarity to central memory CD8+ T cells (Tcm). Such CD8+ T effectors were characterized with abundant surface expression of both Cxcr3 and CD62L and possessed strong stemness. These CD8+ T effectors mainly developed into Tcm in adoptive transfer and exclusively possessed the capacity to generate Tcm in antigen re-stimulation, indicating they functioned to be Tcm precursors. These Cxcr3+CD62L+ Tcm precursors were determined by high expression of T cell transcription factor 1 (TCF-1), which guaranteed CD62L expression by binding to distal enhancers of Sell (gene symbol for CD62L). Cxcr3+CD62L+ Tcm precursors could be massively obtained by expansion of anti-CD3/28 activated CD8+ T cells with low IL-2 plus IL-7, and these in vitro-expanded Cxcr3+CD62L+ Tcm precursors exhibited strong effective in tumor elimination and were better than conventional high IL-2 expanded-CD8+ T effectors for clearance of tumors.

2022-09-07 | GSE212687 | GEO

Cross-presenting CD103+ dendritic cells are protected from influenza virus infection

2013-06-19 | GSE38838 | GEO

Dynamic equilibrium of lung Trm dictates waning immunity after IAV infection

Project description:Lung resident memory (Trm) CD8 T cells induced by influenza A virus (IAV), are pivotal for providing heterosubtypic immunity, but are not maintained long term, causing gradual loss of protection. This contrasts sharply with long-term maintenance of Trm induced by localized infections of the skin and other tissues. Here we show that the decline in lung Trm is determined by an imbalance between apoptosis and lung recruitment/conversion to Trm of circulating memory cells. At the cellular level, circulating effector memory (Tem) rather than central memory (Tcm) cells are the precursors for conversion to lung Trm. Time-dependent changes in expression of genes critical for Trm differentiation together with enrichment of Tcm diminish the capacity of circulating memory CD8 T cells to form Trm, explaining why IAV-induced Trm are not stably maintained over time. Importantly, systemic booster immunization, through increasing the number of circulating Tem cells, induces an increase in lung Trm pool, providing a new rational for future IAV vaccines.

2016-11-18 | GSE86973 | GEO

Transcription profiling of human CD8 naive (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells

Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.

2005-01-01 | E-TABM-40 | biostudies-arrayexpress

Expression of miRNAs in human ex-vivo CD8+ T cell subsets

Project description:The aim was to assess miRNA expression in 3 human ex-vivo CD8+ T cell subsets which span from antigen inexperienced cells (NaM-CM-/ve) to early memory cells (central memory, Tcm) and later stage memory cells (effector memory, Tem) CD8+ T cells were sorted on a FACS Aria II machine. N = naM-CM-/ve = CD8+, CCR7+, CD45RA+, CD45RO-, Tcm = central memory = CD8+, CCR7+, CD45RA-, CD45RO-,Tem= effector memory = CD8+, CCR7-, CD45RA-, CD45RO+ PBMC were isolated from 3 healthy human donors and sorted by FACS into 3 CD8+ T cell subsets. Total RNA was purified using the miRVANA kit (Ambion)

2014-10-24 | E-GEOD-54867 | biostudies-arrayexpress

Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females

Project description:Neuroinflammation in the brain contributes to the pathogenesis of Parkinson’s disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of early-to-mid iPD, especially in females, after analyzing >700 innate and adaptive features. This profile, also reflected by fewer CD8+FOXP3+ regulatory T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated CD8 differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central-memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing previously-unrecognized candidates for early diagnosis and treatments.

2023-10-13 | GSE237254 | GEO

Expression of miRNAs in human ex-vivo CD8+ T cell subsets

Project description:The aim was to assess miRNA expression in 3 human ex-vivo CD8+ T cell subsets which span from antigen inexperienced cells (Naïve) to early memory cells (central memory, Tcm) and later stage memory cells (effector memory, Tem) CD8+ T cells were sorted on a FACS Aria II machine. N = naïve = CD8+, CCR7+, CD45RA+, CD45RO-, Tcm = central memory = CD8+, CCR7+, CD45RA-, CD45RO-,Tem= effector memory = CD8+, CCR7-, CD45RA-, CD45RO+

2014-10-24 | GSE54867 | GEO

Transcriptional responses of antigen-specific CD8 T cells after secondary influenza virus challenge

Project description:To evaluate the transcriptional responses of effector and memory virus-specific CD8 T cell subsets after primary and secondary influenza infection, we sorted subsets of FluNP 366-374/Db+ CD8+ T cells from the BAL, lung, and spleen at the peak of primary x31 influenza infection (day 10), resting memory (day 30), or 3 days after secondary PR8 influenza challenge (Day 30+3). Cells from the circulation were excluded from BAL and lung based on intravital labeling with anti-CD45. Memory cells from the lung were further separated in TRM and TEM subsets based on expression of CD69 at the day 30 and day 30+3 timepoints. Memory cells from the BAL were separated into long-term airway resident versus recently-recruited cells based on CD11a expression at the day 30 and days 30+3 timepoints. The results show that virus-specific BAL and lung TRM cells, but not lung TEM cells or spleen TEM cells, rapidly alter their transcriptional program and increase expression of effector molecules within 3 days of a secondary influenza challenge.

2024-02-15 | GSE247464 | GEO

Identification of a novel human memory T cell population with the characteristics of stem-like stress resistance

Project description:High-dose chemotherapy may kill not only tumor cells but also immunocytes, and frequently induces severe lymphocytopenia. On the other hand, patients who recover from the nadir maintain immunity against infection, suggesting the existence of an unknown memory T cell population with stress-resistance, long-living capacity, proliferation and differentiation. Recently, the differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. Here we report a novel human T cell memory population, âyoung memoryâ T (TYM) cells. TYM cells are defined by positive expression of CD73, which represents high aldehyde dehydrogenase 1 activity and CXCR3 among CD8+CD45RA+CD62L+ T cells. TYM proliferate upon TCR stimulation, with differentiation capacity into TCM and TEM and drug-resistance.Moreover, TYM are involved in memory function for viral and tumor-associated antigens in healthy donors and cancer patients, respectively. Regulation of TYM might be very attractive for peptide vaccination, adoptive cell transfer therapy and haematopoietic stem cell transplantation.

2016-07-01 | E-MTAB-4080 | biostudies-arrayexpress

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