Mohini Gray's research is focused on the pathogenesis of autoimmune rheumatic diseases and understanding immune regulation. We are particularly interested in how this is affected by B cells, the autophagy pathway and alpha defensins.
Autoimmunity: Autoimmune disease results from a breakdown in immune regulation to self-antigens. It is commonly believed that the failure to ingest rapidly, cells dying naturally (apoptotic cells) leads them to spill their nuclear contents, resulting in a break in self-tolerance to these otherwise sequestered antigens. Indeed many autoimmune diseases are characterised by auto-antibodies to nuclear antigens. However it is well established that early in the course of apoptosis these same nuclear antigens are transported to and expressed on the apoptotic cell surface. We have recently discovered that innate-like B cells from the marginal zone (MZB) and peritoneal B1 subsets respond to these nucleosomal complexes expressed on apoptotic cells by secreting the immunosuppressive cytokine IL-10. In humans we find these natural regulatory B cells reside within the CD27+ circulating B cell subset and they also respond to DNA complexes on apoptotic cells (AC) by secreting IL-10. There are two components to this recognition, first the B cells must express a full BCR repertoire, and second they must express Toll-like receptor 9 (TLR9). We have recently discovered that these B cells are self reactive.
We have also discovered that B cells from multidrug resistent Rheumatoid Arthritis patients have a unique profile that may help to define their response to treatment.
The second area of activity in our lab revolves around antimicrobial peptides. We have discovered how they prevent macrophages from generating proteins, whilst still being active against a number of pathogens.
Autoimmunity: We have gathered a large number of samples from patients with autoimmune diseases, which is shedding new light on how immune regulation breaks down, leading to diseases such as rheumatoid arthritis and SLE. In terms of our focus on alpha defensins we have now elucidated their mechanism of action in macrophages and this opens the way to generating peptide mimics that have the potential to treat both autoimmunity and sepsis.
I work as a rheumatologist for 25% of my working week. This has enabled me to collect and archive a large number of clinical specimens from patients with new onset rheumatoid arthritis and other autoimmune diseases such as SLE and Sjogrens syndrome. These samples have started to yield valuable insights into human immunology in health and disease.