Dataset Information

Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]

ABSTRACT: CD4+ regulatory T cells (Tregs) activate and expand in response to many different types of injuries, suggesting that they play a critical role in controlling the host response to tissue damage. Here we use multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. CD44high Tregs expand in response to injury and are more suppressive than CD44low Tregs. T cell receptor (TCR) analysis reveal that CD44high Tregs undergo TCRαβ clonal expansion and increased CDR3 diversity in response to injury. Bulk and single-cell RNA sequencing with paired TCR clonotype analysis demonstrate that important Treg-associated genes were significantly differentially expressed in both CD44high and CD44low Tregs with expanded TCR clonotypes. CyTOF analysis verified protein expression of these genes on CD44high Tregs, with increases in Helios, Galectin-3 and PYCARD expression following injury. Collectively, these data provide new insights into CD44high Tregs, an important subset in the response to injury to tissue damage.

ORGANISM(S): Mus musculus

PROVIDER: GSE174789 | GEO | 2022/05/01

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection. However, despite heightened readiness to respond, memory cells exist in a functionally quiescent state. The paradigm is that memory cells remain inactive due to lack of TCR stimuli. Here we report a unique role of Tregs in orchestrating memory quiescence by inhibiting effector and proliferation programs through CTLA-4. Loss of Tregs resulted in activation of genome-wide transcriptional programs characteristic of potent effectors, and both developing and established memory quickly reverted to a terminally differentiated (KLRG-1hi/IL-7R±lo/GzmBhi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality and protective efficacy. CTLA-4, an inhibitory receptor overexpressed on Tregs, functionally replaced Tregs in trans to rescue Treg-less memory defects and restore homeostasis of secondary mediators as well. These studies present CD28-CTLA-4-CD80/CD86 axis as a novel target to potentially accelerate vaccine-induced immunity and improve T-cell memory quality in current cancer immunotherapies proposing transient Treg-depletion. We used microarray analysis to detail the global programming of gene expression in LCMV GP33-specific CD8 T cells differentiated in the presence or absence of regulatory T cells Differentiation of memory CD8 T cells entails a progressive transition of highly activated effector program to a quiescent memory program. A key question in the field is to understand the factors that aid in the differentiation of memory cells from effector cells. It is a generally accepted paradigm that effector cells transition to a memory state by default after antigen clearance, since TCR stimuli is the key driver of effector programs in CD8 T cells. We hypothesized that the effector to memory transition of CD8 T cells involves active immunological brakes through regulatory T cells (Tregs) that allow the highly activated effector cells to convert into quiescent memory cells. To address this hypothesis, we used FoxP3-DTR mice to deplete Tregs during the window following antigen clearance, during which the effector CD8 T cells convert to long-lived memory cells. To get a deeper understanding of the global transcriptome of CD8 T cells as they transition from an effector to a memory state, we isolated and arrayed the antigen-specific CD8 T cells at day 16 post-infection that have experienced the transitional environment with and without the presence of Tregs.

Dataset Information

Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure