Immunology Select

The immune environment in the gut is maintained by the constant exchange of information between immune cells, epithelial cells, and the gut microbiota. However, when these channels of communication break down the consequences can be dire—chronic inflammation, infection, or diminished nutrient absorption. This Immunology Select explores the response of intestinal epithelial cells to pathogens and the signals that recruit cells of the immune system to the gut during infection and inflammation and in development. Although intestinal epithelial cells are often the first to come in contact with patho-genic organisms in the gut, their roles in marshalling the immune response are only beginning to be understood. Working in mice, Zaph et al. (2007) now provide evidence that the behavior of intestinal epithelial cells is a critical element in mounting an appropriate and effective immune response to infection. They show that the specific loss of IkB kinase-b (IKK-b) in intestinal epithelial cells impairs the clearance of an infection by Trichuris muris, a nematode parasite that is a model for human whipworm infection. IKK-b activates the transcription factor NF-kB and is a critical element of the innate immune response. The authors propose that the primary effect of IKK-b disruption is to alter the communication between intestinal epithelial cells and the antigen-presenting dendritic cells, which in turn affects the character of the T cell response. Typically, the eradication of Trichuris infection requires the differentiation of pathogen specific T helper 2 (T h 2) cells. The authors show that intestinal epithelial cells lacking IKK-b had reduced expression of the cytokine TSLP (thymic stromal lypho-poietin), which suppresses the production of proinflammatory cytokines by dendritic cells, thereby promoting differentiation of T h 2 cells. Thus, these mutant mice were unable to clear the infection, and the enhanced production of proinflammatory cytokines—including IL-12, IL-23, and IFNg— led to severe inflammation. Remarkably , blocking these cytokines using monoclonal antibodies restored the T h 2 response and promoted resistance to infection. These finding reveal that NF-kB activation in intestinal epithelial cells regulates both inflammation and the T cell response. Inflammatory bowel disease is characterized by the infiltration of T cells and neutrophils into the gut and an increase in proinflammatory cytokines, such as IL-17. According to recent work by Qian et al. (2007), the adaptor protein Act1 is a component of the signaling pathway downstream of IL-17 that promotes intestinal inflammation. The authors show that Act1 is recruited to IL-17 …