Welniak L A, Khaled A R, Anver M R, Komschlies K L, Wiltrout R H, Durum S, Ruscetti F R, Blazar B R, Murphy W J
Laboratory of Leukocyte Biology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
J Immunol. 2001 Mar 1;166(5):2924-8. doi: 10.4049/jimmunol.166.5.2923.
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 (IL-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, IL-7R 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 pro-apoptotic 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.
白细胞介素-7（IL-7）是T细胞和B细胞发育过程中的关键细胞因子，但人们对其在非造血细胞上的活性了解甚少。在使用白细胞介素-7受体缺失（IL-7Rα(-/-)）小鼠作为受体的同种异体骨髓移植研究中，发现了一个意外的现象。与野生型IL-7Rα(+/+)小鼠相比，这些小鼠在全身照射后体重减轻更为显著。病理评估表明，IL-7Rα(-/-)受体小鼠的肠道隐窝损伤更严重，这表明这些小鼠可能更容易发生肠道破坏。因此，我们确定了预处理本身对这些小鼠肠道的影响。对IL-7Rα(-/-)小鼠和IL-7Rα(+/+)小鼠进行照射，并检查小肠内的损伤和细胞凋亡情况。在濒死动物中，IL-7Rα(-/-)小鼠的小肠有广泛损伤，包括在1500 cGy全身照射后隐窝明显缺失和绒毛极度缩短。相比之下，照射后8天，IL-7Rα(+/+)小鼠的小肠已再生，表现为绒毛长度正常和隐窝增生。在750 cGy照射后，IL-7Rα(-/-)小鼠隐窝中的凋亡细胞比例更高，同时肠道上皮细胞中促凋亡蛋白Bak的表达也随之增加。这些结果表明，IL-7Rα(-/-)小鼠隐窝内肠道干细胞的放射敏感性增加，且IL-7在保护这些相同细胞免受辐射诱导的凋亡中发挥作用。本研究描述了IL-7在非造血组织中的一种新作用。
