p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome.
p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome.
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p53抑制肠上皮细胞对MHC II类分子的呈递以防止辐射诱导的胃肠道综合征
DOI：
10.1038/s41467-023-44390-w
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发表时间：
2024-01-02
影响因子：
16.6
通讯作者：
Hu, Wenwei
中科院分区：
文献类型：
--
作者：
Wang, Jianming;Chang, Chun-Yuan;Yang, Xue;Zhou, Fan;Liu, Juan;Bargonetti, Jill;Zhang, Lanjing;Xie, Ping;Feng, Zhaohui;Hu, Wenwei
放射引起的胃肠综合征是放射治疗的主要并发症和限制因素。肿瘤抑制因子p53在辐射诱导的胃肠道毒性中具有保护作用。然而，其潜在机制尚不清楚。在这里，我们报告了调节IL12-p40/MHC II类信号通路是p53保护免受辐射诱导的胃肠道综合征的关键机制。p53抑制炎症细胞因子IL12-p40的表达，进而抑制肠上皮细胞上MHCⅱ类的表达，从而抑制T细胞活化和辐照后引起肠道干细胞损伤的炎症反应。抗il12 -p40中和抗体可抑制炎症，恢复p53缺陷小鼠辐照后肠上皮再生缺陷，延长小鼠生存期。这些结果揭示了IL12-p40/MHC II类信号通路介导p53在确保肠道干细胞功能和适当的免疫反应以应对辐射保护粘膜上皮方面的重要作用，并提出了一种潜在的治疗策略来保护辐射诱导的胃肠道综合征。放射诱导的胃肠道综合征是放疗的并发症，肿瘤抑制因子p53参与保护胃肠道毒性。Wang和他的同事们发现，p53对辐射诱发的胃肠道综合征的保护作用涉及肠道干细胞功能和通过IL12- p40/MHC-II轴抑制辐射引发的炎症。
Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome. Radiation induced gastrointestinal syndrome is a complication of radiotherapy and the tumor suppressor p53 is implicated in protection from gastrointestinal toxicity. Here Wang and colleagues show that p53 protection against radiation-induced gastrointestinal syndrome involves intestinal stem cell function and inhibition of inflammation triggered by radiation via the IL12- p40/MHC-II axis.
影响因子：
3.8
作者：
Reuter BK;Zhang XJ;Miller MJ
通讯作者：
Miller MJ
影响因子：
5.6
作者：
Persa E;Szatmári T;Sáfrány G;Lumniczky K
通讯作者：
Lumniczky K