Control of innate and anti-tumour immunity by mononuclear phagocytes

The innate immune system is the first line of defense against invading pathogens and tumours. Dendritic cells, monocytes, macrophages, and natural killer cells are key cells of the innate immune system, clearing microbial infections as well as tumours. These cells are activated by signalling via pattern recognition receptors that recognize pathogen associated molecular patterns. Down-stream signalling leads to the initiation of antimicrobial and inflammatory responses. Any deviation in the receptor signalling, development, or interactions of these cells can result in an inappropriate immune response, potentially leading to either immunodeficiencies (the inability to clear infections) or chronic inflammatory diseases. Lyn tyrosine kinase is an important enzyme in establishing signalling thresholds in leukocytes. Previous research in mice has shown that alterations in the activity of this protein affect the magnitude of the immune response, and that autoimmune diseases develop when it is absent. Manreet Chehal is investigating this further, determining whether increases and decreases in Lyn activity alter the development of innate immune cells and the responses of specific immune cells to pathogens and tumours. Her preliminary results indicate that an increase in Lyn activity enhances the innate immune response, including increased dendritic cell activation of natural killer cells. Chehal hopes to show that the immune response to pathogens and tumours depends on Lyn activity. Ultimately, her work could contribute to the development of new therapies that target the Lyn pathway to control inflammatory and autoimmune diseases or increase the body’s own natural defenses.