Gastrointestinal cells of IL-7 receptor null mice exhibit increased sensitivity to irradiation

IL-7 is a critical cytokine in the development of T and B cells but little is known about its activity on nonhematopoietic cells. An unexpected finding was noted in allogeneic bone marrow transplant studies using IL-7 receptor null (LL-7R alpha (-/-)) mice as recipients. These mice exhibited a significantly greater weight loss after total body irradiation compared with wild type, IL-7R alpha (+/+), mice. Pathological assessment indicated greater intestinal crypt damage in IL-7R alpha (-/-) recipients, suggesting these mice may be predisposed to gut destruction. Therefore, we determined the effect of the conditioning itself on the intestinal tract of these mice. IL- 7R(alpha-/-) mice and IL-7R alpha (+/+) mice were irradiated and examined for lesions and apoptosis within the small intestine, In moribund animals, LL-7 alpha (-/-) mice had extensive damage in the small intestine, including marked ablation of the crypts and extreme shortening of villi following 1500 cGy total body irradiation. In contrast, by 8 days after irradiation, the small intestines of IL-7R alpha (+/+) mice had regenerated as distinguished by normal villus length and hyperplastic crypts, Following 750 cGy irradiation, IL-7R alpha (-/-) mice had a higher proportion of apoptotic cells in the crypts and an accompanying increase in the proapoptotic protein Bak was expressed in intestinal epithelial cells. These results demonstrate the increased radiosensitivity of intestinal stem cells within the crypts in IL-7R alpha (-/-) mice and a role for IL-7 in the protection of radiation-induced apoptosis in these same cells. This study describes a novel role of IL-7 in nonhematopoietic tissues.

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