AUTHOR=Sawyer Andrew J. , Garand Mathieu , Chaussabel Damien , Feng Carl G. 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.634119

DOI=10.3389/fimmu.2021.634119

ISSN=1664-3224

ABSTRACT=<p>Cystatin F encoded by <italic>CST7</italic> is a cysteine peptidase inhibitor known to be expressed in natural killer (NK) and CD8<sup>+</sup> 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 <italic>CST7</italic> is upregulated in the blood during a diverse set of infectious and non-infectious inflammatory conditions. Interestingly, this upregulation of <italic>CST7</italic> was neutrophil-specific, as its expression was unchanged in NK and CD8<sup>+</sup> T cells during sepsis. Further analysis demonstrated that known microbial products or cytokines commonly associated with inflammation failed to increase <italic>CST7</italic> 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 <italic>CST7</italic> 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.</p>