PlumX Metrics
Embed PlumX Metrics

Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits

bioRxiv, ISSN: 2692-8205
2020
  • 6
    Citations
  • 0
    Usage
  • 0
    Captures
  • 1
    Mentions
  • 19
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    6
    • Citation Indexes
      6
      • CrossRef
        6
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    19
    • Shares, Likes & Comments
      19
      • Facebook
        19

Most Recent News

Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans

Abstract Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired

Article Description

Interleukin 2 (IL-2) is a key homeostatic cytokine, with potential therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical application has been hampered by pleiotropic functionality and wide-spread receptor expression, with unexpected adverse events during trials. To characterize the IL-2 homeostatic network, we developed a novel mouse strain allowing IL-2 production to be diverted. Rewiring of IL-2 production to diverse leukocyte sources allowed the identification of contextual influences over IL-2 impact. Network analysis identified a priority access for Tregs, and a competitive fitness cost induced among both Tregs and conventional CD4 T cells for IL-2 production. CD8 T cells and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified the Treg circuit, while IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8 Tregs and ILC2 cells. The former was associated with an unexpected concentration of rare CD8 Tregs in B cell zones, while the latter drove a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain unexpected adverse effects observed during clinical trials of exogenous IL-2. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.

Bibliographic Details

Carly E. Whyte; Kailash Singh; Oliver T. Burton; Meryem Aloulou; Alena Moudra; Carlos P. Roca; Francisco J. Naranjo; Lubna Kouser; James Dooley; Adrian Liston; Susan Schlenner; Félix Lombard-Vadnais; Sylvie Lesage; Tino Hochepied; Timotheus Y.F. Halim

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know