The emerging role of IL-22 as a potential radiosensitivity biomarker for radiation-induced intestinal injury

Considering the beneficial role played by IL-22 in alleviating radiation-induced intestinal injury through its promotion of epithelial regeneration, it was hypothesized that individuals with elevated IL-22 levels might display either minimal intestinal injury or increased resistance following ionizing irradiation exposure. To assess the impact of IL-22 on intestinal radiosensitivity, IL-22 expression levels was detected in serum of normal mice. Mice naturally with high or low levels of IL-22 or pretreated with IL-22 or anti-IL-22 were subjected to 10 Gy of total abdominal radiation (TAI). Daily observation, morphometric analysis, quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and western blot were employed to measure weight loss, survival rate, cell proliferation and death, and DNA damage. Furthermore, influence of IL-22 pretreatment on survival of intestinal organoid exposed to 6 Gy X-rays was evaluated. The results showed that IL-22 expression levels were varied between individuals. Surprisingly, mice with high IL-22 levels displayed exacerbated intestinal injury manifesting as increased weight loss, reduced regeneration capacity and more cell apoptosis. Notably, a strong positive correlation between weight loss and IL-22 expression level was observed. Additionally, pretreatment with IL-22 resulted in increased mortality accompanied by enhanced cell apoptosis and DNA damage in crypt of early exposure, as well as diminished survival of intestinal organoid, while pretreatment with anti-IL-22 antibody alleviated the intestinal injury. In this study, we established a direct link between IL-22 and radiosensitivity, suggesting IL-22 could be used as a potential biomarker for predicting individual intestinal radiosensitivity prior to radiation exposure.