Modeling cell-cell communication for immune systems across space and time.

Communicating is crucial for cells to coordinate their behaviors. Immunological processes, involving diverse cytokines and cell types, are ideal for developing frameworks for modeling coordinated behaviors of cells. Here, we review recent studies that combine modeling and experiments to reveal how immune systems use autocrine, paracrine, and juxtacrine signals to achieve behaviors such as controlling population densities and hair regenerations. We explain that models are useful because one can computationally vary numerous parameters, in experimentally infeasible ways, to evaluate alternate immunological responses. For each model, we focus on the length-scales and time-scales involved and explain why integrating multiple length-scales and time-scales in a model remain challenging. We suggest promising modeling strategies for meeting this challenge and their practical consequences.