Identification of Human Immune Cell Subtypes Most Vulnerable to IL-1ß-induced Inflammatory Signaling Using Mass Cytometry

Hema Kothari; Corey M. Williams; Chantel McSkimming; Mythili Vigneshwar; Eli R. Zunder; Coleen A. McNamara

Cytokine storm is suspected of producing the overzealous immune response driving the severe cardiopulmonary complications that are fueling the high morbidity and mortality rates in certain COVID-19-infected individuals 1, 2 . Cytokine storm or macrophage activation syndrome or secondary haemophagocytic lyphohistocytosis has previously been described as a serious complication in other clinical contexts including individuals with rheumatologic disorders such as systemic onset juvenile inflammatory arthritis also known as Still's disease 3 , sepsis 4 , and CAR-T cell therapy 5 . IL-1β is one of the key inflammatory cytokines implicated in the cytokine storm syndrome 4, 6, 7 . Inhibition of IL-1βinduced cellular signaling with the IL-1 receptor (IL-1R) antagonist, Anakinra, has shown promise in treating cytokine storm and is proposed as a potential therapy for subjects with this severe complication of COVID-19 [8] [9] [10] 11 . Yet, little is known about the immune cell subtypes most vulnerable to IL-1βinduced inflammatory signals in humans. New technologies, such as mass cytometry (CyTOF), have emerged as powerful analytic tools to identify unique cell phenotypes associated with specific inflammatory stimuli and their inhibitors [12] [13] [14] . CyTOF uses antibodies conjugated to isotopes of rareearth metals not found in human cells, so it eliminates background signal and minimizes signal overlap, allowing for the identification of a greater number of proteins that more precisely define cellular identify and activation states. These novel, customized approaches hold promise for the discovery of the cellular mechanisms mediating IL-1β-induced pathologies and the identification of sensitive and specific biomarkers that could be used to assist in early identification of cytokine storm and those who may response to specific therapies such as IL-1β or IL-1R inhibitors.