Quorum sensing via dynamic cytokine signaling comprehensively explains divergent patterns of effector choice among helper T cells

by Edward C. Schrom II, Simon A. Levin, Andrea L. Graham In the animal kingdom, various forms of swarming enable groups of autonomous individuals to transform uncertain information into unified decisions which are probabilistically beneficial. Crossing scales from individual to group decisions requires dynamically accumulating signals among individuals. In striking parallel, the mammalian immune system is also a group of decentralized autonomous units (i.e. cells) which collectively navigate uncertainty with the help of dynamically accumulating signals (i.e. cytokines). Therefore, we apply techniques of understanding swarm behavior to a decision-m aking problem in the mammalian immune system, namely effector choice among CD4+ T helper (Th) cells. We find that incorporating dynamic cytokine signaling into a simple model of Th differentiation comprehensively explains divergent observations of this process. The plasticity and heterogeneity of in dividual Th cells, the tunable mixtures of effector types that can be generatedin vitro, and the polarized yet updateable group effector commitment often observedin vivo are all explained by the same set of underlying molecular rules. These rules reveal that Th cells harness dynamic cytokine signaling to implement a system of quorum sensing. Quorum sensing, in turn, may confer adaptive advantages on the mammalian immune system, especially during coinfection and during coevolution with manipulative parasites. This highlights a new way of...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research