The project is utilizing the method of conditional gene targeting in the mouse in order to dissect the cytokine network particularly in the gut associated lymphatic tissue. We are focusing on the cytokine IL-10. IL-10 is essential for the proper control of the gut-associated immune system as it can prevent the establishment of a chronic inflammatory bowel disease in mice. Up to now we could show that T cell derived IL-10 is one of the central regulators of the gut associated immune system as mice in which T cell derived IL-10 was experimentally eliminated develop a chronic inflammatory bowel disease. As the T cells are only one subset of many cell types in the gut, which is capable of producing IL-10 we are now eliminating IL-10 production from other cell types in order to follow the development of an inflammatory bowel disease. Besides this, we are also dissecting the role of IL-10 responding cells in the gut-associated immune system by conditionally inactivating the IL-10 receptor gene in different cell types. The cytokine network consists of other cytokines, which can control the IL-10 system. We therefore extend our study by the generation and analysis of conditional mice for the IL-12 and the interferon gamma receptor genes.