J Leukoc Biol. 2026 Jun 4:qiag068. doi: 10.1093/jleuko/qiag068. Online ahead of print.
ABSTRACT
Glucocorticoids (GCs) are used as anti-inflammatory and immunosuppressive drugs in many immune mediated diseases, but their use in sepsis and shock is controversial. This is caused in part by a lack of information regarding the responding cell types and GC-regulated genes in vivo. We used large collections of public blood transcriptomic datasets and different GC-induced query genes to obtain 2 robust gene expression correlation signatures of GC induction, either in the absence or in the presence of severe inflammation. GC signature 1 originated from circadian cortisol with biases for gene expression in NK cells and neutrophils. GC signature 2 originated from GC in severe inflammation, mainly with biases for gene expression in monocytes and neutrophils. Many genes upregulated by GC treatment in septic shock and burn shock were also present as high-ranking genes in GC signatures, which pointed to their direct regulation by GC. Robust GC signatures were also obtained from dataset collections of different tissues for comparison, and of monocytes and neutrophils, separately. Gene induction by GC was put into a wider framework of gene expression in circulating monocytes and neutrophils in health and during systemic inflammation, which included macrophage-like cells and a hypoxia-related gene expression signature in monocytes in severe inflammation. We present and interpret a large number of GC-regulated genes in different blood cells and tissues in vivo, and select 2 whole blood transcriptomic biomarker gene sets, GC-1 and GC-2, for monitoring cortisol action in health, and in severe inflammation, respectively.
PMID:42241654 | DOI:10.1093/jleuko/qiag068