Scleroglucan protects the intestine from irradiation-induced injury by targeting the IL-17 signaling pathway

• Published in: International immunopharmacology 2024-03, Vol.129, p.111614-111614, Article 111614
• Main Authors: Huang, Daqian, Wang, Yuedong, Zhai, Xuanlu, Shen, Qiaofeng, Zhang, Liao, Fang, Duo, Fang, Lan, Zhang, Jianyi, Ma, Yuejun, Chu, Chen, Liu, Guanbo, Cheng, Ying, Liu, Cong, Du, Jicong, Cai, Jianming
• Format: Article
• Language: English
• Subjects: IL-17 signaling pathway; Immune cells; Intestinal stem cells; Radiation intestinal injury; Scleroglucan
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111614

[Display omitted] •Scleroglucan alleviates IR-induced intestinal damage in mice and promotes regeneration of ISCs after IR.•Scleroglucan activates the immune system and significantly up-regulated serum immune factors and immune cells.•Scleroglucan significantly activated the IL-17 and NF-κB signaling pathways and promoted the proliferation of ISCs after IR by up-regulating Th17 and IL-17A.•Inhibition of IL-17 signaling pathway weakens the radiation protection effect of Scleroglucan and ttenuates Scleroglucan's immune-activating function. Intestinal tissue is extremely sensitive to ionizing radiation (IR), which is easy to cause intestinal radiation sickness, and the mortality rate is very high after exposure. Recent studies have found that intestinal immune cells and intestinal stem cells (ISCs) may play a key role in IR-induced intestinal injury. C57BL6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Scleroglucan (125.0 mg/kg) or Anti-mouse IL-17A –InVivo (10 mg/kg), the number of mice in each group was n ≥ 3.Survival time, body weight, pathology, organoids and immune cell markers of the mice after IR (10.0 Gy) were compared, and the mechanism of action in intestinal tissues was verified by transcriptome sequencing. Scleroglucan has significant radiation protective effects on the intestine, including improving the survival rate of irradiated mice, inhibiting the radiation damage of intestinal tissue, and promoting the proliferation and differentiation of intestinal stem cells (ISCs). The results of RNA sequencing suggested that Scleroglucan could significantly activate the immune system and up-regulate the IL-17 and NF-κB signaling pathways. Flow cytometry showed that Scleroglucan could significantly up-regulate the number of Th17 cells and the level of IL-17A in the gut. IL-17A provides radiation protection. After intraperitoneal injection of Scleroglucan and Anti-mouse IL-17A -InVivo, mice can significantly reverse the radiation protection effect of Scleroglucan, down-regulate the molecular markers of intestinal stem cells and the associated markers of DC, Th1 and Th17 cells, and up-regulate the associated markers of Treg and Macrophage cells. Scleroglucan may promote the proliferation and regeneration of ISCs by regulating the activation of intestinal immune function mediated by IL-17 signaling pathway and play a protective role in IR-induced injury.