尿石素A激活肠上皮细胞中的芳香烃受体-NLRP6介导通路，以调节黏膜免疫并增强肠道屏障完整性
Urolithin A activates aryl hydrocarbon receptor-NLRP6-mediated pathways in intestinal epithelial cells to modulate mucosal immunity and strengthen gut barrier integrity.
摘要(中文译文)
芳香烃受体（AHR）在炎症性肠病（IBD）发病机制中，对肠道屏障和黏膜免疫功能的协调发挥核心作用。然而，不同配体激活AHR会产生不同的结果，介导这些效应的下游通路仍不清楚。在此，我们报道，微生物代谢产物尿石素A（UroA）选择性激活小鼠肠上皮细胞（IEC）中的AHR，触发含NOD样受体热蛋白结构域蛋白6（NLRP6）炎症小体，导致白细胞介素（IL）-18而非IL-1β的释放。进一步，我们发现UroA诱导IEC产生的IL-18对于IL-22、黏蛋白2和REG3γ的产生以及抵御结肠炎至关重要。此外，在IBD患者的肠道活检组织中，UroA分别显著上调IEC中IL-18和3型先天淋巴细胞中IL-22的水平。这些结果表明，UroA激活AHR通过NLRP6-IL-18-IL-22通路调节健康和IBD条件下的肠道屏障功能。
Abstract
The aryl hydrocarbon receptor (AHR) plays a central role in orchestrating gut barrier and mucosal immune functions in the pathogenesis of inflammatory bowel disease (IBD). Nevertheless, activation of the AHR by diverse ligands yields varied outcomes, and the downstream pathways responsible for these effects remain unknown. Here, we report that selective activation of AHR in mouse intestinal epithelial cells (IEC) by the microbial metabolite, urolithin A (UroA), triggers the Nod-like receptor pyrin domain-containing protein 6 (NLRP6) inflammasome, resulting in the release of interleukin (IL)-18 but not IL-1β. Further, we show that UroA-induced IL-18 in IECs is critical for IL-22, mucin 2 and REG3γ production, as well as protection against colitis. Moreover, UroA significantly upregulates IL-18 and IL-22 levels in IECs and type-3 innate lymphoid cells, respectively, in intestinal biopsies from patients with IBD patients. These results demonstrate that activation of AHR by UroA modulates intestinal barrier function through an NLRP6-IL-18-IL-22 pathway in both healthy and IBD conditions.
如何引用
AMA
Sweta Ghosh, Zachary M Vanwinkle, Sobha Rani Bodduluri, Subir Kumar Juin, Mahendar Kadari, Ankita Singh, et al. Urolithin A activates aryl hydrocarbon receptor-NLRP6-mediated pathways in intestinal epithelial cells to modulate mucosal immunity and strengthen gut barrier integrity.. Nature communications. 2026; doi:10.1038/s41467-026-73760-3.
APA
Sweta Ghosh, Zachary M Vanwinkle, Sobha Rani Bodduluri, Subir Kumar Juin, Mahendar Kadari, Ankita Singh, et al (2026). Urolithin A activates aryl hydrocarbon receptor-NLRP6-mediated pathways in intestinal epithelial cells to modulate mucosal immunity and strengthen gut barrier integrity.. Nature communications. https://doi.org/10.1038/s41467-026-73760-3
GB/T 7714
Sweta Ghosh, Zachary M Vanwinkle, Sobha Rani Bodduluri, Subir Kumar Juin, Mahendar Kadari, Ankita Singh, et al. Urolithin A activates aryl hydrocarbon receptor-NLRP6-mediated pathways in intestinal epithelial cells to modulate mucosal immunity and strengthen gut barrier integrity.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73760-3.
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