The language of cytokines: Decoding immune signals with information theory

Communication between cells is fundamental for maintaining and restoring homeostasis in multicellular organisms under both physiological and pathological conditions. A variety of mechanisms for encoding, transmitting, and decoding information have evolved. Information theory, originally developed in engineering, has been increasingly applied to dissect how cells process and exchange signals. Yet, biological systems exhibit distinctive properties that pose conceptual and quantitative challenges not encountered in technical systems. In this review, we examine how cellular networks manage and often exploit the intrinsic heterogeneity of cell populations. We discuss how individual cells and cell populations sense cytokine stimulus strength and specificity, and how regulatory proteins shape not only signalling dynamics but also the capacity and robustness of information transmission. From an information theoretical perspective, health can be viewed as a state of efficient and reliable cellular communication, whereas disease reflects the loss or distortion of robust cellular communication. We conclude that information theory offers an intuitive framework for biologists seeking to unravel the principles of cytokine signalling.