Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets.
Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs). Unexpectedly, ablation of IL-2R signaling in cTregs resulted in increased proliferation, expression of eTreg genes, and enhanced capacity to develop into eTregs. Thus, IL-2R signaling normally acts as a checkpoint to maintain cTreg homeostasis while restraining their development into eTregs. Loss of IL-2R signaling also alters the distribution of eTreg subsets, with increased IFNγR1+ eTregs and CXCR5+ PD-1+ T follicular regulatory (TFR) cells but decreased intestinal RORγt+ TR17 cells. These changes lower eTreg suppressive function supporting expansion of IFNγ-secreting T effector cells. Thus, IL-2R signaling also safeguards Treg function and licenses differentiation of specialized eTregs.
Pubmed ID: 39759017 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
- CRAN (RRID:SCR_003005)
- Jackson Laboratory (RRID:SCR_004633)
- UCSC Genome Browser (RRID:SCR_005780)
- QIAGEN (RRID:SCR_008539)
- BD Biosciences (RRID:SCR_013311)
- ggplot2 (RRID:SCR_014601)
- HISAT2 (RRID:SCR_015530)
- Kaluza (RRID:SCR_016182)
- clustree (RRID:SCR_016293)
- Illumina NovaSeq 6000 Sequencing System (RRID:SCR_016387)
- clusterProfiler (RRID:SCR_016884)
- Morpheus by Broad Institute (RRID:SCR_017386)
- Agilent 2100 Bioanalyzer Instrument (RRID:SCR_018043)
- 10X Genomics Chromium Plus Genetic Analyzer (RRID:SCR_019326)
- Cytek Aurora Spectral Analyzer (RRID:SCR_019826)
- Beckman Coulter CytoFLEX LX Flow Cytometer (RRID:SCR_025067)
- C57BL/6J (RRID:IMSR_JAX:000664)
Antibodies used in this publication
None foundAssociated grants
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This is a list of tools and resources that we have found mentioned in this publication.
CRAN (tool)
RRID:SCR_003005
Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.
View all literature mentionsJackson Laboratory (tool)
RRID:SCR_004633
An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
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RRID:SCR_005780
Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.
View all literature mentionsQIAGEN (tool)
RRID:SCR_008539
A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
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RRID:SCR_014601
Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
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RRID:SCR_015530
Graph-based alignment of next generation sequencing reads to a population of genomes.
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RRID:SCR_016293
Software package which allows to produce clustering trees and visualize clusterings at different resolutions. Used in the analysis of large data sets to group together samples with similar properties.
View all literature mentionsIllumina NovaSeq 6000 Sequencing System (tool)
RRID:SCR_016387
System unleashes groundbreaking innovations that leverage our proven technology. Now you can get scalable throughput and flexibility for virtually any sequencing method, genome, and scale of project.
View all literature mentionsclusterProfiler (tool)
RRID:SCR_016884
Software R package for statistical analysis and visualization of functional profiles for genes and gene clusters.
View all literature mentionsMorpheus by Broad Institute (tool)
RRID:SCR_017386
Software tool for versatile matrix visualization and analysis. Program to generate heatmaps from input data. JavaScript matrix visualization and analysis.
View all literature mentionsAgilent 2100 Bioanalyzer Instrument (tool)
RRID:SCR_018043
Bioanalyzer system is automated electrophoresis tool that providesa nalytical evaluation of various samples types in many workflows, including next generation sequencing NGS, gene expression, biopharmaceutical, and gene editing research. Digital data is provided in timely manner and delivers assessment of sizing, quantitation, integrity and purity from DNA, RNA, and proteins. Minimal sample volumes are required for accurate result, and data may be exported in many different formats.
View all literature mentions10X Genomics Chromium Plus Genetic Analyzer (tool)
RRID:SCR_019326
Genetic analyzer, referred to as Chromium Controller for combining large partition numbers with a diverse barcode library to generate >100,000 barcode-containing partitions.
View all literature mentionsCytek Aurora Spectral Analyzer (tool)
RRID:SCR_019826
Prodigy incorporating a combination of patent-pending technologies that takes flow cytometry to the next level of performance and flexibility. With up to five lasers, three scattering channels, and 64 fluorescence channels, the Aurora suits every laboratory's needs, from to high complexity applications. A paradigm shifting optical design provides unprecedented flexibility, enabling the use of a wide array of new fluorochrome combinations without reconfiguring your system for each application. The state-of-the-art optics and low-noise electronics provide excellent sensitivity and resolution. Flat-top beam profiles, combined with a ly designed fluidics system, translate to outstanding performance at high sample flow rates.
View all literature mentionsBeckman Coulter CytoFLEX LX Flow Cytometer (tool)
RRID:SCR_025067
This model is equipped with four lasers (405, 488 561 and 638nm), and is capable of detecting FSC, SSC and 16 colors.
View all literature mentionsC57BL/6J (tool)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
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