Transcriptomic Profiling Identifies Neutrophil-Specific Upregulation of Cystatin F as a Marker of Acute Inflammation in Humans.

Cystatin F encoded by is a cysteine peptidase inhibitor known to be expressed in natural killer (NK) and CD8 T cells during steady-state conditions. However, little is known about its expression during inflammatory disease states in humans. We have developed an analytic approach capable of not only identifying previously poorly characterized disease-associated genes but also defining regulatory mechanisms controlling their expression. By exploring multiple cohorts of public transcriptome data comprising 43 individual datasets, we showed that is upregulated in the blood during a diverse set of infectious and non-infectious inflammatory conditions. Interestingly, this upregulation of was neutrophil-specific, as its expression was unchanged in NK and CD8 T cells during sepsis. Further analysis demonstrated that known microbial products or cytokines commonly associated with inflammation failed to increase expression, suggesting that its expression in neutrophils is induced by an endogenous serum factor commonly present in human inflammatory conditions. Overall, through the identification of upregulation as a marker of acute inflammation in humans, our study demonstrates the value of publicly available transcriptome data in knowledge generation and potential biomarker discovery.