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

BioRxiv : the Preprint Server for Biology
Hema KothariC. A. McNamara

Abstract

IL-1{beta} has emerged as a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19 and blockade of the IL-1 receptor (IL-1R) with Anakinra has entered clinical trials in COVID-19 subjects. Yet, knowledge of the specific immune cell subsets targeted by IL-1{beta} and IL-1{beta}-induced signaling pathways in humans is limited. Utilizing mass cytometry (CyTOF) of human peripheral blood mononuclear cells, we identified effector memory CD4 T cells and CD4-CD8low/-CD161+ T cells as the circulating immune subtypes with the greatest expression of p-NF-{kappa}B in response to IL-1{beta} stimulation. Notably, CCR6 distinctly identified T cells most responsive to IL-1{beta}. Other subsets including CD11c myeloid dendritic cells (mDCs), classical monocytes (CM), two subsets of natural killer cells (CD16-CD56brightCD161- and CD16-CD56dimCD161+) and a population of lineage- (Lin-) cells expressing CD161 and CD25 also showed IL-1{beta}-induced expression of p-NF-{kappa}B. The IL-1R antagonist, Anakinra significantly inhibited IL-1{beta}-induced p-NF-{kappa}B in the CCR6+ T cells and CD11c mDCs with a trending inhibition in CD14 monocytes and Lin-CD161+CD25+ cells. IL-1{beta} also induced a rapid but much less ...Continue Reading

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