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Glucocorticoid-driven gene expression in circulating monocytes and neutrophils in health and severe inflammation

Arthur Molendijk1, Leo Koenderman2

  • 1Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht 3584 CX, the Netherlands.

Journal of Leukocyte Biology
|June 4, 2026
PubMed

Insights

Glucocorticoids (GCs) impact immune cells differently depending on inflammation. This study identifies two gene signatures (GC-1 and GC-2) to monitor GC effects in blood, aiding treatment decisions.

Area of Science:

  • Immunology
  • Genomics
  • Pharmacology

Background:

  • Glucocorticoids (GCs) are widely used anti-inflammatory and immunosuppressive drugs.
  • Their efficacy and safety in sepsis and shock remain controversial due to limited understanding of cellular responses and gene regulation in vivo.
  • Identifying specific GC-regulated genes and cell types is crucial for optimizing their use.

Purpose of the Study:

  • To identify robust gene expression signatures of glucocorticoid (GC) induction in vivo.
  • To characterize GC-regulated genes and responding cell types in both healthy and inflamed states.
  • To develop transcriptomic biomarker gene sets for monitoring GC action.

Main Methods:

  • Analysis of large public blood transcriptomic datasets.
  • Utilized query genes related to GC induction under varying inflammatory conditions.
  • Developed gene expression correlation signatures (GC signature 1 and GC signature 2).
  • Compared whole blood signatures with tissue-specific and cell-specific datasets (monocytes, neutrophils).

Main Results:

  • Identified two distinct GC-induced gene expression signatures: GC signature 1 (circadian cortisol, NK cells, neutrophils) and GC signature 2 (severe inflammation, monocytes, neutrophils).
  • Found significant overlap between upregulated genes in GC-treated septic and burn shock patients and the derived GC signatures, suggesting direct GC regulation.
  • Established GC signatures in various tissues and isolated monocytes/neutrophils, providing a broader framework of GC effects in health and inflammation.

Conclusions:

  • GCs exert distinct regulatory effects on different blood cell types, varying with inflammatory status.
  • Developed two whole blood transcriptomic biomarker gene sets (GC-1 and GC-2) for monitoring cortisol action in health and severe inflammation, respectively.
  • These signatures offer valuable tools for understanding GC mechanisms and guiding clinical applications in immune-mediated diseases and critical illness.
Keywords:
gene expressionglucocorticoidmonocyteneutrophilsepsis

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