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

Intriguingly, the only cell type where the majority of the cells showed expression of p-NF-kB after IL-1β stimulation was a subset of CD161 + cells (cluster 17) that were Lin -(CD3 -CD4 -CD8 -CD19 -CD14 -CD16 -HLA-DR -CD123 -) and expressed much higher levels of CD25 than the CD56 bright NK cells (cluster 3) (Supplementary Figs. 10b,c) . Moreover, the majority (~80%) of the cells in cluster 17 were CD56 -. Interestingly, cluster 17 showed a robust induction of p-NF-kB, p-p38 as well as activation of STAT1, STAT3 and STAT5 at later time points. Human innate lymphoid cells (ILCs) also express CD161 89 and Ohne et al. 22 demonstrated that IL-1β plays a critical role in inducing proliferation, cytokine production, maturation and plasticity of human ILC2. IL-1β mediated these effects in combination with IL-2 and/or IL-12, and NF-kB inhibition blocked IL-1β-induced responses 22 . Notably, p-NF-kB + cells within our cluster 17 bear resemblance to the phenotype of the ILC2. Consistent with the higher expression of CD127 in the ILC2 cells as compared to the CD56 bright NK cells as shown by Ohne et al., 22 the p-NF-kB + cells within cluster 17 expressed higher CD127 than the p-NF-kB + cells within the CD56 bright NK cells (cluster 3) (Supplementary Fig. 10d) . However, in contrast to the ILC2, around 20-30% of the p-NF-kB + cells within cluster 17 were found to be CD56 dim (Supplementary Figs. 10e,f) .