Stochastic Secretion Response to Transient Stimulus of Group-2 Innate Lymphoid Cells (ILC2)

Cellular activities are not only heterogeneous between each single cell, but also fluctuate over time. Our novel method enabled us to visualize secretion in single-cell resolution in real-time [1]. Using this method, we have already discovered that individual group-2 innate lymphoid cells (ILC2) start secretion at very different times one by one after being stimulated with interleukin (IL)-2 and 33. However, it had almost been unclear that how the cells sense and respond to transiently changeable extracellular environments, since we had only tested the continuous stimulus. Here, we analyzed the secretion response of ILC2 against different duration of transient stimuluses. As we shortened the duration of IL-33 stimulus to 90, 60, and 30 minutes, the smaller portion of the cells secreted. The cells started secretion within only three hours after these short stimuluses. On the other hand, some cells initiated secretion even eight hours after the addition of the continuous stimulus. In addition, the cells gradually suspended secretion after the stimulus was removed, while the cells tended to continue secretion if the stimulus existed. These results suggested the dual characteristics of the secretion response of ILC2: the cells might stochastically respond to the addition of stimulus and slowly initiated secretion, but quickly aborted secretion once the stimulus disappeared.