Androgen Signaling in Type 2 Innate Lymphoid Cells Drives Sex Differences in Helicobacter-Induced Gastric Inflammation and Atrophy

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Abstract Background & Aims Gastric cancer is the fifth most common worldwide. Men are disproportionately affected by gastric cancer, which ranks as fourth in men compared to eighth women Chronic inflammation driven Helicobacter pylori infection remains leading risk factor. Emerging evidence suggests that sex hormones modulate immune responses, contributing differences outcomes and susceptibility. This study investigates how androgens influence inflammatory response contribute disparities disease progression. Methods Male female C57BL/6 mice were colonized with felis investigate inflammation. Androgen levels manipulated bilateral castration males dihydrotestosterone (DHT) treatment females. Single-cell RNA sequencing was used identify androgen-responsive leukocyte populations establish cell communication networks between clusters. The functional roles of these cells further defined using ILC2- T cell-deficient mouse models. Results Infected developed significantly more severe inflammation, atrophy, metaplasia males. depletion increased accelerated preneoplastic lesion development, while pathological features reduced DHT treatment. Androgen-responsive type 2 innate lymphoid (ILC2s) key initiators ILC2 abolished H. pathogenesis. Conclusions reveals suppress -induced modulating activation. We found protective, androgen exacerbated development. These findings provide mechanistic insight into age-related increase male incidence, coinciding declining levels. Our results suggest circulating concentrations may serve a prognostic biomarker for men. Graphical

Язык: Английский

Xinkai Kujiang Treatment Improves Gastrointestinal Microbiota and Inhibits the Il-17 Signaling Pathway to Ameliorate Spasmolytic Polypeptide Expressing Metaplasia in Mice

Опубликована: Янв. 1, 2025

Язык: Английский

Emerging role of spasmolytic polypeptide-expressing metaplasia in gastric cancer

Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 15(6), С. 2673 - 2683

Опубликована: Дек. 1, 2024

Gastric cancer (GC) ranks among the top five most diagnosed cancers globally, with particularly high incidence and mortality rates observed in Asian regions. Despite certain advancements achieved through early screening treatment strategies many countries, GC continues to pose a significant public health challenge. Approximately 20% of patients infected Helicobacter pylori develop precancerous lesions, which metaplasia is critical. Except for intestinal (IM), characterized by goblet cells appearing stomach glands, one type mucous cell metaplasia, spasmolytic polypeptide-expressing (SPEM), has attracted much attention. SPEM represents specific epithelial alteration within gastric mucosa, expressing trefoil factor 2 (TFF2) basal resembling deep antral gland cells. It primarily arises from transdifferentiation mature chief cells, neck (MNCs), or isthmus stem commonly regarded as precursor lesion development inflammation subsequent carcinogenesis. The formation intricately associated chronic inflammation, infection, various other environmental genetic factors. Recently, profound exploration biological molecular mechanisms underlying SPEM, deeper understanding its role initiation progression emerged. This review summarizes role, mechanisms, clinical significance onset GC.

Язык: Английский