We are interested in intestinal immune regulation in inflammatory bowel disease and graft-versus-host disease. The central hypothesis of our laboratory is that local and systemic autoimmunity can be regulated by intestinal immune conditioning. We utilize helminths as tools to condition intestinal immune system. In mouse graft-versus-host disease (GVHD) and inflammatory bowel disease (IBD) models, we explore the mechanisms of immune regulation by helminth-induced intestinal immune conditioning.

Therapeutic use of helminths to modulate intestinal immunity is based on hygiene hypothesis, which proposes that the rising incidence and prevalence of autoimmune, allergic and immunological disorders is due to lack of exposure to environmental commensal or residential organisms in our current hygienic life style. Certain helminthic parasites belong to these commensal and residential organisms. Hygienic life style involves practices, such as chlorination of water, pasteurization of milk, vaccination and use of antibiotics. Although hygienic life style has dramatically reduced the rate of infectious diseases, it has also prevented our exposure to commensal and residential organisms that humans had been exposed throughout evolution and that appear to be critical to the development of a healthy immune system. Our group has expanded these observations on hygiene hypothesis to bone marrow transplantation where intestinal helminths participate in teaching the transplanted donor immune cells to discriminate the “new-self” from the “new-nonself” in the recipient. At cellular and molecular level, we work on helminthic induction of T helper 2 (Th2) pathway and immune regulatory cytokine, TGFβ, particularly in mucosal T lymphocytes. TGFβ is essential to trigger various immune regulatory pathways, such as Foxp3 positive regulatory T cells (Treg). We work on the hypothesis that intestinal immune conditioning through helminths or helminth products may induce Tregs in vivo, prevent GVHD and improve the outcome of bone marrow transplantation.