Research Interests The central focus of the laboratory is on the regulation of mucosal immune responses, particularly the mucosal immune response to the microbiota, which represent the largest mass of antigen encountered by the immune system. The cellular and molecular mechanisms that maintain mucosal immune homeostasis are being defined. When these mechanisms fail, pathogenic effector T cells are generated that result in colitis. We have cloned a set of immunodominant antigens of the microbiota that stimulate such pathogenic T cells and result in inflammatory bowel disease. Among these cloned antigens, previously unknown bacterial flagellins have emerged as a major cluster. Seroreactivity to these flagellins is found in multiple experimental models of colitis in mice and in half of patients with Crohn's disease. These antigens drive a newly described CD4 T cell effector subset making IL-17 (Th17) which appears to be responsible for disease progression. A T cell receptor transgenic mouse reactive to CBir1 flagellin has been generated and is being used to study the innate and adaptive immune response to these microbiota antigens. A second major effort is in the identification of T reg cells in the intestine that recognize microbial antigens and maintain homeostasis. The mechanisms whereby such cells are induced are being defined and the application of these cells to prevent or treat intestinal inflammation is being tested. Lastly, a microbiota antigen microarray has been constructed which can be used to analyze serologic reactivity to the microbiota in both mouse and human. Sera from various human populations are presently being analyzed.