Gut reactions: immune pathways in the intestine in health and disease

During my biochemistry degree I became fascinated by the complexity and wonder of the immune system. How in the vast majority of us it steadfastly protects from pathogens but in others, it turns on our own tissues or innocuous environmental antigens leading to autoimmune and chronic inflammatory diseases. It is evident that on the one hand, the immune system is vital for human health but that when dysregulated also has the capacity to kill the host. It is evident that on the one hand, the immune system is vital for human health but that when dysregulated also has the capacity to kill the host. We now know that alongside other mechanisms of self‐tolerance functionally specialized regulatory T cells (Treg) play a non‐redundant role in controlling the immune response to both self‐ and environmental antigens. In this perspective, I describe my early work that contributed to the discovery of Treg and our more recent focus on elucidation of their function in intestinal homeostasis.After a brief spell in the City of London as an accountant, I was lucky enough to land a PhD position in Don Masons' Lab in the Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford. The CIU was headed by the dynamic and brilliant Alan Williams who, with Neil Barclay, discovered the Ig superfamily of leukocyte surface proteins. The Oxford group had produced a large series of monoclonal antibodies (mAbs) against cell surface proteins. These tools revolutionized the study of immune cells allowing the molecular characterization of cell surface proteins, as well as the description of markers that could distinguish functional immune subsets. With a mAb termed OX‐22 (which recognized an isoform of CD45) in hand, I was able to build on work ongoing in Don's Lab to show that this antibody subdivided rat …