Integration of IL-2 and IL-4 signals coordinates divergent regulatory T cell responses and drives therapeutic efficacy.

The immune system is essential to defend our bodies from attacks of microbial invaders. It contains many types of cells that communicate with each other through proteins called cytokines. Cytokines act as messages that can promote or suppress the immune response. Since several types of immune cells can exist within the same environment, many different signals are sent simultaneously, from which each individual cell must tease out the correct message. So far, it has been unclear how cells decode simultaneous messages, which may be key for improving therapeutics for inflammatory diseases. To investigate this, Zhou et al. studied the effect of two cytokines (IL-2 and IL-4) on a major type of suppressive immune cell called regulatory T cell or Treg. This revealed that when Tregs grown in the laboratory were simultaneously exposed to IL-2 and IL-4, the cytokine duo boosted the production of new Tregs much more than using either cytokine alone. Together, the cytokines also increased the production of another cytokine (IL-10), and over time, Treg cells producing IL-10 divided more frequently, leading to an even more robust ability to suppress overactive immune responses. Zhou et al. then validated the experiments in cells using mouse models of asthma and multiple sclerosis. Treatment with an IL-2 and IL-4 cytokine cocktail not only prevented but reversed the symptoms of the diseases to a greater extent than either cytokine alone, suggesting that this could be a significantly improved therapy for patients affected by these conditions. This study provides important insights into how cytokines can work together to substantially improve the activity of immune cells and reduce inflammation. It also introduces a promising new treatment strategy to dampen or even eliminate a range of devastating symptoms caused by inflammatory diseases.