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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.19.047274 doi: bioRxiv preprint This novel comprehensive atlas of IL-1β-induced signaling in circulating human immune cells provides new insights into the cell types most vulnerable to IL-1β activation and the timing of these effects in humans. Together, these provide key data for the study and design of more targeted approaches to chronic inflammatory diseases that may lessen adverse effects. Moreover, our work has clear implications for the development of immune phenotypic approaches to identify COVID-19 subjects at higher risk of cytokine storm and those most likely to benefit from therapies targeting IL-1β or its downstream mediators such as IL-6. Garcia Borrega, J. 1. IL-1β induces rapid expression of p-NF-kB and p-p38 in distinct immune cell subtypes. a, CyTOF antibody panel. Note: markers including chemokine receptors, CD161, CD11b, CD11c and others are expressed on more than one cell type. b, Experimental design. c, SPADE analysis was performed using cell surface markers to identify 200 cell clusters using 10% down-sampling. SPADE tree showing median expression (blue to red depicting low to high) of the indicated lineage markers. The size of each node is proportional to the number of cells in that population. d, 9 immune cell types were identified: Total T cells were identified as CD3 + , and subsets as CD4 + , CD8 + and CD4 -CD8 low , B cells as CD19 + , NK cells as CD56 + CD16 + , monocyte subsets as HLA-DR + CD14 + and HLA-DR + CD16 + and DCs as HLA-DR + CD11c + and HLA-DR + CD123 + . Scale: Color blue to red within each cluster corresponds to low to high cell count. e, Representative SPADE tree from a donor showing IL-1β-induced expression of p-NF-kB, p-p38 and p-ERK. Note: the scale min and max depicting median expression differ for each phospho marker. author/funder. All rights reserved. No reuse allowed without permission.