Subproject B15N

Interleukin-7 (IL-7) is of central importance for the development and survival of numerous immune cells. The impaired action of IL-7 is associated with severe immune defects while its overexpression is associated with immune cell hyperactivation and autoimmunity. The development of gastrointestinal inflammation is frequently associated with dysregulated IL-7 production and the IL-7-dependent activation of pathogenic T cells. In this context, the blockade of the IL-7/IL-7R signaling pathway is discussed as a therapeutic option to treat gastrointestinal inflammation. While the importance of IL-7 for the development of the immune system and the maintenance of immunological self-tolerance is well documented, it is largely unknown how IL-7 production is regulated in vivo. Furthermore, it is unclear whether IL-7 affects the biology of non-immune cells. However, this knowledge is of crucial importance for the development of new therapies aiming at the manipulation of the IL-7/IL-7R signaling pathway. Recently, we have generated an IL-7 reporter mouse. With the help of this mouse we could show that IL-7 regulates intestinal homeostasis at multiple levels. Whether these IL-7-dependent effects result from the direct action of IL-7 on the intestinal epithelium is unclear. To answer this question, we will make use of conditional knock out mice in which intestinal epithelial cells are insensitive to IL-7. Our aim is to clarify by which molecular and cellular mechanisms IL-7 regulates intestinal homeostasis under physiological and pathophysiological conditions.