Our immune systems function by employing two separate responses when in contact with disease. The first is the innate immune system, which aids in monitoring for infection throughout the body. Innate immunity is more generalizable and will trigger immune cells to neutralize the pathogen. Adaptive immunity is the second barrier of defense, which is stronger and more specific. The adaptive immune response occurs after innate immunity signals that a disease is present and comprises of T and B cells. Although the two are separate systems, they work together to fight off disease. Additionally, there are subtypes of T and B cells that help maintain healthy immunity, such as regulatory T cells (Tregs). Specifically, Tregs are cells that regulate immune homeostasis and inflammation. These cells have a specialized function that suppress other lymphocytes from attacking healthy cells and tissue. They are integral in preventing autoimmune disorders and aiding in tissue repair. Tregs can be implicated in many different diseases, but scientists are continually working to understand their role in immune surveillance.
A recent article in Nature Communications, by Dr. Martin Turner and others, demonstrate that a group or family of proteins that aid in the regulation of RNA function are critical to maintain healthy immunity. Turner is a professor and leads the Immunology research program at the Babraham Institute. He is also the Associate Director for Research Strategy and focuses on molecular processes that control the development and function of immune cells. More specifically, he investigates cell surface markers and their associated intracellular signaling.
The RNA binding proteins (RBPs) that the team investigated are part of the Zinc Finger Protein 36 (ZFP36) family. Previous work by Turners group identified ZFP36 as critical proteins in the differentiation and activity of T cells. However, their role in Treg function was unclear.
Since Tregs are crucial for maintaining the immune system and regulating inflammation, researchers wanted to investigate Treg function in aging. Specifically, how do Tregs change with age-related inflammation. RBPs, including ZFP36, are responsible for many roles in regulating RNA such as modulating stability, degradation, and others. To learn more about how ZFP36 proteins affect Tregs, researchers deleted these ZFP36 genes in Tregs. Researchers found that mice with Tregs lacking these genes had increased inflammation, expanded immune cells, and elevated proteins that trigger immune responses. Further investigation revealed that ZFP36 genes regulate other genes that help Tregs maintain immune homeostasis. Turner and his group realized that ZFP36 genes also allowed Tregs to respond to special proteins referred to as interleukin 2 (IL2) and 7 (IL7), which also regulate immune response.
The discovery that ZFP36 genes play an important role in maintaining Treg function is paradigm shifting. It has previously been unclear how Tregs maintain their activity and regulate immunity. Additionally, the discovery that specific gene expression is necessary for Tregs to respond to IL2 and IL7 implicates these genes as critical regulators necessary for healthy immune maintenance. As a result, this discovery has the potential to improve therapeutic strategies in various diseases and prolong patient survival.
Article, Nature Communications, Martin Turner, Babraham Institute
