IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis

IL-7 is a stromal cell-derived cytokine with a well-established physiologic role in lymphocyte biology. This report describes an unexpected role for IL-7 in the development of colitis in a T and B cell-deficient environment. Recombination-activating gene-2 (RAG-2)-deficient mice (RAG-2(-/-)) were exposed to and subsequently maintained a horizontally transmitted microbial flora that included Helicobacter hepaticus. These animals mounted a strong myeloid cell response and developed both systemic and local signs of a severe colitis. A striking infiltration of F4/80 and MHC class II-positive cells was seen in the colon and cecum of animals undergoing the disease. Mice mutant for both IL-7 and RAG-2 (IL-7/RAG-2(-/-)) that were colonized by the same flora showed no signs of myeloid responses or colitis, indicating that IL-7 plays a critical role in exacerbating a non-T cell/non-B cell-mediated chronic inflammatory response. Recombinant IL-10 protein therapy was able to prevent the occurrence of colitis in susceptible mice, suggesting a pivotal role for macrophages. The implications of a role for IL-7 in this disease model with respect to human inflammatory bowel disease are discussed.