ArticleGastroenterology2021
Glucocorticoids and Androgens Protect From Gastric Metaplasia by Suppressing Group 2 Innate Lymphoid Cell Activation.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Global research trends in signaling pathways of spasmolytic polypeptide-expressing metaplasia pathogenesis: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- The origins and progression of pyloric metaplasia following gastric mucosal injury.Physiological reviews · 2026Review
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Multi-omics analysis reveals AR as a potential prognostic factor and immune-related therapeutic target in gastric cancer.Biochemistry and biophysics reports · 2026Article
- Gastric intestinal metaplasia: unraveling the multifactorial pathogenesis and advancing risk stratification for gastric cancer prevention.Cellular and molecular life sciences : CMLS · 2026Review
- ILC2-derived IL-9 activates regulatory T cells to facilitate post-myocardial infarction repair.Cell communication and signaling : CCS · 2026Article
- Roles of interleukins in spasmolytic polypeptide‑expressing metaplasia (Review).International journal of oncology · 2026Review
- The gut-liver axis modulates intestinal immune homeostasis.Mucosal immunology · 2026Review
- Immune modulation by sex hormones: unveiling the complex interplay and regulatory networks.Frontiers in immunology · 2026Review
- Autoimmune gastritis: a comprehensive review of pathophysiology, risk stratification, and management.Frontiers in immunology · 2026Review
- Listening to the Past, Shaping the Future: A Data-mining Based and Visual Analysis of Five Decades of Gastric Carcinogenesis Research.Biological procedures online · 2025Article
- IL33-ST2 axis is a predictive biomarker for anti-PD1 therapeutic efficacy in advanced gastric cancer.Journal of translational medicine · 2025Article
- Revolutionizing Gastric Cancer Prevention: Novel Insights on Gastric Mucosal Inflammation-Cancer Transformation and Chinese Medicine.Chinese journal of integrative medicine · 2025Review
- LAMP2-FLOT2 interaction enhances autophagosome-lysosome fusion to protect the septic heart in response to ILC2.Autophagy · 2025Article
- ARID1A mutation drives gastric tumorigenesis via activating type 2 immune dominant microenvironment.iScience · 2025Article
- Article
- New perspectives on gastric disorders: the relationship between innate lymphoid cells and microbes in the stomach.Cellular and molecular life sciences : CMLS · 2025Review
- Alcoholic brain injury is a modifiable risk factor: natural active substance intervention promises to improve alcohol-induced cognitive impairment.Frontiers in nutrition · 2025Review
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7 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe immune compartment is critical for maintaining tissue homeostasis. A weak immune response increases susceptibility to infection, but immune hyperactivation causes tissue damage, and chronic inflammation may lead to cancer development. In the stomach, inflammation damages the gastric glands and drives the development of potentially preneoplastic metaplasia. Glucocorticoids are potent anti-inflammatory steroid hormones that are required to suppress gastric inflammation and metaplasia. However, these hormones function differently in males and females. Here, we investigate the impact of sex on the regulation of gastric inflammation.
methodsEndogenous glucocorticoids and male sex hormones were removed from mice using adrenalectomy and castration, respectively. Mice were treated with 5α-dihydrotestosterone (DHT) to test the effects of androgens on regulating gastric inflammation. Single-cell RNA sequencing of gastric leukocytes was used to identify the leukocyte populations that were the direct targets of androgen signaling. Type 2 innate lymphoid cells (ILC2s) were depleted by treatment with CD90.2 antibodies.
resultsWe show that adrenalectomized female mice develop spontaneous gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM) but that the stomachs of adrenalectomized male mice remain quantitatively normal. Simultaneous depletion of glucocorticoids and sex hormones abolished the male-protective effects and triggered spontaneous pathogenic gastric inflammation and SPEM. Treatment of female mice with DHT prevented gastric inflammation and SPEM development when administered concurrent with adrenalectomy and also reversed the pathology when administered after disease onset. Single-cell RNAseq of gastric leukocytes revealed that ILC2s expressed abundant levels of both the glucocorticoid receptor (Gr) and androgen receptor (Ar). We demonstrated that DHT treatment potently suppressed the expression of the proinflammatory cytokines Il13 and Csf2 by ILC2s. Moreover, ILC2 depletion protected the stomach from SPEM development.
conclusionsHere, we report a novel mechanism by which glucocorticoids and androgens exert overlapping effects to regulate gastric inflammation. Androgen signaling within ILC2s prevents their pathogenic activation by suppressing the transcription of proinflammatory cytokines. This work revealed a critical role for sex hormones in regulating gastric inflammation and metaplasia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.