Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Step-wise signal integration governs adaptive programming of lymphocytes [scRNA-seq]

ABSTRACT: Lymphocyte differentiation depends on activation via antigen and cytokines during the immune response to infection. How the timing and integration of these signals program the epigenetic and functional fate of these cells is not completely understood. In this study, we find that inflammatory cytokine signals received by innate and adaptive lymphocytes have a context-dependent role for immune memory formation. Without preceding and sufficient antigen receptor signaling, inflammatory cytokines drive terminal differentiation into short-lived effector cells. In contrast, sufficient antigen-receptor signaling redirects inflammatory cytokine signals to promote memory differentiation via cooperation of STAT and AP-1 transcription factors. By this crucial epigenetic mechanism, optimally equipped lymphocytes are selected for memory formation rather than a terminal effector cell fate. Whereas T cells are hardwired to be shielded from premature inflammatory signals, NK cells rely on coincidental early antigen receptor signaling for adaptive responses. Together, step-wise integration of antigen and cytokine signaling optimizes both effector and memory differentiation, allowing for promiscuous recruitment into the acute immune response while promoting avidity maturation in memory populations of both innate and adaptive lymphocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE292296 | GEO | 2026/01/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Step-wise signal integration governs adaptive programming of lymphocytes [bulkRNA-seq and ATAC-seq 6hr Stim]

Project description:Lymphocyte differentiation depends on activation via antigen and cytokines during the immune response to infection. How the timing and integration of these signals program the epigenetic and functional fate of these cells is not completely understood. In this study, we find that inflammatory cytokine signals received by innate and adaptive lymphocytes have a context-dependent role for immune memory formation. Without preceding and sufficient antigen receptor signaling, inflammatory cytokines drive terminal differentiation into short-lived effector cells. In contrast, sufficient antigen-receptor signaling redirects inflammatory cytokine signals to promote memory differentiation via cooperation of STAT and AP-1 transcription factors. By this crucial epigenetic mechanism, optimally equipped lymphocytes are selected for memory formation rather than a terminal effector cell fate. Whereas T cells are hardwired to be shielded from premature inflammatory signals, NK cells rely on coincidental early antigen receptor signaling for adaptive responses. Together, step-wise integration of antigen and cytokine signaling optimizes both effector and memory differentiation, allowing for promiscuous recruitment into the acute immune response while promoting avidity maturation in memory populations of both innate and adaptive lymphocytes.

2026-01-22 | GSE309245 | GEO

Step-wise epigenetic signal integration governs adaptive programming of cytotoxic lymphocytes [CUT&RUN STAT1 STAT5 cJun]

2026-01-22 | GSE308415 | GEO

Step-wise epigenetic signal integration governs adaptive programming of cytotoxic lymphocytes [ATAC-seq AP1inhibitor]

2026-01-22 | GSE308414 | GEO

Step-wise signal integration governs adaptive programming of lymphocytes [CUT&RUN STAT4]

2026-01-22 | GSE292293 | GEO

Step-wise signal integration governs adaptive programming of lymphocytes [bulkRNA-seq and ATAC-seq]

2026-01-22 | GSE292377 | GEO

Transcription factor EB sets the stage for fate decisions of antigen-primed B cells in the absence and presence of co-stimulation

Project description:Ligation of the B cell antigen receptor (BCR) initiates humoral immunity. However, mere BCR signaling without appropriate co-stimulation commits B cells to death rather than to differentiation into immune effector cells. How BCR activation depletes potentially autoreactive B cells while simultaneously primes for receiving rescue and differentiation signals from cognate T lymphocytes remains unknown. Here, using a mass spectrometry-based proteomic approach to identify cytosolic/nuclear shuttling elements, we uncover transcription factor EB (TFEB) as a central BCR-controlled rheostat that drives activation-induced apoptosis, and concurrently, promotes the reception of co-stimulatory rescue signals by supporting B cell migration and antigen presentation. CD40 co-stimulation prevents TFEB-driven cell death, while enhancing and prolonging TFEB’s nuclear residency, which hallmarks antigenic experience also of memory B cells. In mice, TFEB shapes the transcriptional landscape of germinal center B cells. Within the germinal center, TFEB facilitates the dark zone entry of light-zone-residing centrocytes through regulation of chemokine receptors and, by balancing the expression of Bcl-2/BH3-only family members, integrates antigen-induced apoptosis with T cell-provided CD40 survival signals. Thus, TFEB reprograms antigen-primed germinal center B cells for cell fate decisions.

2024-08-08 | PXD054505 | Pride

A microRNA-directed program of cytotoxic CD8+ T cell differentiation

Project description:Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTL, and that deletion or depletion of Dicer in mouse or human activated CD8+ T cells causes upregulation of perforin, granzyme and effector cytokines. Genome-wide analysis of miRNA changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of a miRNA network that controls perforin, eomesodermin (Eomes) and IL-2Ra expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation and antigenic stimulation. Overall our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation. Comparison of control and Dicer knock-out CTLs differentiated in vitro; Comparison of wild type CTLs differentiated in vitro with or without inflammatory stimuli; Comparison of effector and memory precursor CTLs isolated from mice infected with LCMV-Armstrong

2013-12-02 | E-GEOD-51393 | biostudies-arrayexpress

T cell receptor-triggered nuclear actin network formation drives CD4 T cell effector functions

Project description:T cell antigen receptor (TCR) signaling triggers selective cytokine expression to drive T cell proliferation and differentiation required for immune defense and surveillance. The nuclear signaling events responsible for specificity in cytokine gene expression upon T cell activation are largely unknown. Here, we uncover formation of a dynamic actin filament network in the nucleus that regulates cytokine expression for effector functions of CD4 T lymphocytes. TCR engagement triggers the rapid and transient formation of a nuclear actin filament network via nuclear Arp2/3 complex, induced by elevated nuclear Ca2+ levels and regulated via N-Wasp and NIK. Specific interference with TCR-induced formation of nuclear actin filaments impairs production of effector cytokines and prevents generation of antigen-specific antibodies, but does not interfere with immune synapse formation and cell proliferation. Ca2+-regulated actin polymerization in the nucleus allows CD4 T cells the rapid conversion of TCR signals into effector functions required for T cell help Identification of nuclear F-actin sensitive genes upon TCR signaling

2018-11-15 | GSE122531 | GEO

Proteomics of Day 6 IL-2 or IL-15 expanded wild-type and Pim1/Pim2 double knockout CD8+ T cells.

Project description:T cell antigen-receptor (TCR) and cytokine receptor engagement trigger large changes in Serine/Threonine kinase signalling networks to drive T cell activation and differentiation. The role of only few kinase signalling pathways have been studied in detail, and in this context, Pim kinases are an interesting, yet understudied, family of Serine/Threonine kinases, with reported roles in key processes including survival, proliferation, metabolism across a range of cell types. T lymphocytes predominantly express PIM1 and PIM2, which are rapidly induced by TCR, costimulation and cytokine signalling. Using high-resolution mass spectrometry and RNAseq we systematically examine the impact of Pim1/Pim2 double deficiency on in vitro differentiated cytotoxic T lymphocytes (CTL) expanded in the cytokines IL-2 and IL-15 to generate effector or memory T cells respectively. We find that Pim kinases are dispensable for IL-15-driven memory cell differentiation, but that Pim1/2-deficiency has a selective impact on the transcriptome and proteome of IL-2 driven effector CD8 T cells. ~75% of Pim kinase-regulated proteins were not predicted by differences in mRNA in IL-2 expanded CTL. These included proteins that are key for effector cell function: glucose transporters SLC2A1 and SLC2A3 and key effector molecules Granzyme A and B. We find that Pim kinases have this effect via control of protein translation. Another key finding was that the mRNA for key T cell homing receptors Ccr7, S1pr1 and CD62L was increased in Pim1/2-deficienct T cells and that this functionally enhancing homing to secondary lymphoid organs.

2024-04-15 | PXD051213 | Pride

Compartment resolved reference map from highly purified naive, activated, effector and memory CD8+ cells

Project description:Differentiation of CD8+ T lymphocytes into effector and memory cells is key for an adequate immune response and relies on complex interplay of pathways that convey signals from cell surface to nucleus. In this study, we fractionated four CD8+ T cell subtypes; naÃ¯ve, recently activated effector, effector and memory cells into membrane, cytosol, soluble nucleus, chromatin-bound and cytoskeleton compartments. Using LC-MS/MS analysis, identified peptides were matched to human peptides/proteins (SwissProt). Compartment fractionation and gel-LC-MS separation identified 2399 proteins in total. Among these 735 were detected in all five, 241 in four, 257 in three, 368 in two and 798 found in only one fraction. Comparison between the two most different subsets, naÃ¯ve and effector, yielded 146 significantly regulated proteins.

2016-02-29 | MSV000079540 | MassIVE

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