SUCCESSFUL allergy and infection therapies may be possible following recent insights into the development and function of newly discovered Type 1 regulatory (Tr1) cells. With these cells having an immunosuppressive function, scientists believe manipulating them could provide effective therapy for many immune dysregulation disorders.
A recent study identified the crucial role of the ITK enzyme in the development of Tr1 cells. The team used genetically modified mice to create three study samples: mice with active Tr1 cells, Tr1 cells with an inhibited ITK enzyme, and Tr1 cells with no ITK enzyme. The mice were also bred so their Tr1 cells glowed green when they developed, in order to make monitoring easy.
The results of the study highlighted the importance of ITK; in both the mice with blocked ITK and those lacking ITK altogether, the Tr1 cells failed to develop. This finding was also replicated when human blood cells were used, indicating the potential of novel therapeutics designed to target this enzyme and manipulate the Tr1 development pathway. During a second experiment, the researchers identified another critical enzyme in this pathway, IRF4, and confirmed its presence in humans. This transcription factor also proved key for controlling the development of Tr1 cells, thus providing another target for manipulation of these valuable immune cells.
“The more we understand about how these cells develop, the signals and pathways they use, the more likely we will be able to devise approaches to manipulate them,” elucidated Prof Avery August, Cornell’s College of Veterinary Medicine, Ithaca, New York, USA. The researchers propose this study will have important implications for the treatment of many immune-related diseases. Firstly, drugs that enhance Tr1 cell production and hence suppress the overactive immune response to an allergen may provide successful allergy therapies. In contrast, new treatments for viral and bacterial infections and tumours may be possible by selectively blocking the development of Tr1 cells, reducing immune suppression and allowing patients to recover faster.
Looking to the future, the research team commented on the importance of balancing Tr1 cell numbers to ensure the immune system effectively targets invading pathogens without causing damaging pathology during the immune response. The team hope to implement these findings and find out whether they can successfully fine-tune the function of Tr1 cells.