The human and murine immune systems: regulated by dichotomous molecules

In this review, the important and dichotomous role of several receptors, inflammatory mediators and cells in the fine-tuning of immune responses in humans and mice is discussed. The underappreciated dichotomy of at least some molecules of the immune system, like PD-1, Gasdermin D and several cytokines, leads to unpredictable outcomes, especially when these molecules are targeted or manipulated for the treatment of distinct diseases. In this sense, this manuscript aims to highlight that, under particular situations, macromolecules involved in proinflammatory responses might lead to anti-inflammatory effects and vice versa. Understanding the mechanisms involved in this dichotomy might lead to specific therapies under certain conditions and/or important new molecular targets for the treatment of many diseases, minimizing collateral effects. In conclusion, this manuscript underscores how the immune system is controlled by the fine balance between the dichotomous effects of single molecules, depending on the circumstances.