Immune regulation and pathology
Our aims are to understand immunity and diseases, particularly those associated with abnormal antibody production. Inadequate or excessive immune responses lead to immunodeficiency or autoimmune and inflammatory diseases, which place a major economic and social burden on world health and the quality of human life. So we are interested in:
1. Immune function and why it varies.
2. Targeting the immune response in autoimmune disease and cancer.
3. Classifying and treating disease in individuals based on molecular pathology.
B cell development: modelling immunodeficiency. Much of our knowledge about immune control has come from studying rare mouse and human mutations. Congratulations to Consuelo, our senior postdoc, for her study on a human immunodeficiency caused by deficiency in a zinc transporter ZIP7, which has been published here in Anzilotti et al, Nature Immunology. This was a collaboration with many groups, but primarily with Sophie Hambleton in Newcastle University, Jean-Laurent Casanova and Mary Ellen Conley at Rockefeller University in New York.
B cell selection: modelling autoimmunity and self-tolerance. We use transgenic models and other basic immunological assays to study antigen-specific B cells. This approach makes it possible for us to compare uniform populations of cells from mice with specific mutations affecting lymphocyte regulation, and track the response to foreign antigens and movement of antigen-specific cells in vivo. Current projects investigate how the immune system regulates the response to different forms of antigen and how B cells are positively selected into the naïve repertoire during ontogeny.
Immune Regulation: developing novel therapeutics. Our final approach is to develop novel antibody-based therapeutics, which will reduce the immune or inflammatory response in human disease. This project, which is a longstanding collaboration with Professor Simon Davis at Oxford, targets superagonists against human leukocyte inhibitory receptors. To accelerate this work, we have developed a series of mice carrying human receptors.