2026-06-23 バース大学
＜関連情報＞
- https://www.bath.ac.uk/announcements/research-highlighting-estrogen-link-could-explain-why-women-are-more-likely-to-suffer-from-crohns/
- https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003766
エストロゲンはNOD2依存性腸内恒常性調節に影響を与える Estrogen impacts NOD2-dependent regulation of intestinal homeostasis
Mckenna Eklund,Edan Foley
PLOS Biology Published: June 9, 2026
DOI:https://doi.org/10.1371/journal.pbio.3003766
Abstract
Mutations in the innate immune receptor NOD2 are the greatest single genetic risk factor for Crohn’s disease, yet the mechanisms by which NOD2 regulates intestinal homeostasis remain unclear. We used a CRISPR-generated zebrafish model to determine the impacts of NOD2 deficiency on intestinal health. In cellular, molecular, and transcriptomic studies, we uncovered substantial effects of NOD2 deficiency on epithelial and immune compartments, including deregulated expression of developmental pathways that establish and maintain the gut epithelium, and an unexpected increase in the expression of multiple estrogen-response genes. In functional assays, we uncovered a mechanistic link between estrogenic signals and NOD2-deficiency phenotypes, whereby exposure to estrogen alone replicated the effects of NOD2-deficiency, and treatment with the estrogen receptor modulator tamoxifen reverted the epithelial defects observed in nod2 mutants. Our findings identify a NOD2-estrogen regulatory axis that supports intestinal homeostasis and suggest that hormonal signaling may contribute to sex-specific aspects of Crohn’s disease.
