Mechanisms of T_REG cell adaptation to inflammation

Inflammation is an important defense mechanism. In this complex and dynamic process, drastic changes in the tissue micro-environment play key roles in dictating the nature of the evolving immune response. However, uncontrolled inflammation is detrimental, leading to unwanted cellular damage, loss of physiological functions, and even death. As such, the immune system possesses tools to limit inflammation while ensuring rapid and effective clearance of the inflammatory trigger. Foxp3⁺ regulatory T (T_REG ) cells, a potently immunosuppressive CD4⁺ T cell subset, play a crucial role in immune tolerance by controlling the extent of the response to self and non-self Ags, all-the-while promoting a quick return to immune homeostasis. T_REG cells adapt to changes in the local micro-environment enabling them to migrate, proliferate, survive, differentiate, and tailor their suppressive ability at inflamed sites. Several inflammation-associated factors can impact T_REG cell functional adaptation in situ including locally released alarmins, oxygen availability, tissue acidity and osmolarity and nutrient availability. Here, we review some of these key signals and pathways that control the adaptation of T_REG cell function in inflammatory settings.