A tissue injury sensing and repair pathway distinct from host pathogen defense.
A tissue injury sensing and repair pathway distinct from host pathogen defense.
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DOI：
10.1016/j.cell.2023.03.031
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发表时间：
2023-05-11
期刊：
影响因子：
64.5
通讯作者：
Fuchs, Elaine
中科院分区：
文献类型：
--
作者：
Liu, Siqi;Hur, Yun Ha;Cai, Xin;Cong, Qian;Yang, Yihao;Xu, Chiwei;Bilate, Angelina M.;Gonzales, Kevin Andrew Uy;Parigi, S. Martina;Cowley, Christopher J.;Hurwitz, Brian;Luo, Ji-Dung;Tseng, Tiffany;Gur-Cohen, Shiri;Sribour, Megan;Omelchenko, Tatiana;Levorse, John;Pasolli, Hilda Amalia;Thompson, Craig B.;Mucida, Daniel;Fuchs, Elaine
病原体感染和组织损伤是破坏体内平衡的普遍损伤。先天免疫感测微生物感染并诱导细胞因子/趋化因子以激活抗性机制。在这里，我们表明，与大多数病原体诱导的细胞因子相反，白细胞介素-24（IL-24）主要由组织损伤后的屏障上皮祖细胞诱导，并且独立于微生物组或适应性免疫。此外，小鼠中的IL 24消融不仅阻碍表皮增殖和再上皮化，而且阻碍真皮伤口床内的毛细血管和成纤维细胞再生。相反，异位IL-24诱导的稳态表皮触发全球上皮间充质组织修复反应。在机制上，IL-24表达依赖于上皮IL-24受体/STAT 3信号传导和缺氧稳定，其在损伤后会聚以触发涉及IL-24介导的受体信号传导和代谢调节的自分泌和旁分泌信号传导。因此，与病原体的先天免疫感测以解决感染平行，上皮干细胞感测损伤信号以协调IL-24介导的组织修复。上皮干细胞感测损伤信号以激活IL-24介导的组织修复途径，该途径在分子上与先天免疫中病原体诱导的IFN信号传导不同，但在功能上平行。
Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections and induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast to most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after tissue injury and is independent of microbiome or adaptive immunity. Moreover, Il24 ablation in mice impedes not only epidermal proliferation and re-epithelialization but also capillary and fibroblast regeneration within the dermal wound bed. Conversely, ectopic IL-24 induction in the homeostatic epidermis triggers global epithelial-mesenchymal tissue repair responses. Mechanistically, Il24 expression depends upon both epithelial IL24-receptor/STAT3 signaling and hypoxia-stabilized , which converge following injury to trigger autocrine and paracrine signaling involving IL-24-mediated receptor signaling and metabolic regulation. Thus, parallel to innate immune sensing of pathogens to resolve infections, epithelial stem cells sense injury signals to orchestrate IL-24-mediated tissue repair. Epithelial stem cells sense injury signals to activate an IL-24-mediated tissue repair pathway that is molecularly distinct but functionally parallel to pathogen-induced IFN signaling in innate immunity.
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影响因子：
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