ArticleBasic & clinical pharmacology & toxicology2021
RORγt inhibitor SR1001 alleviates acute pancreatitis by suppressing pancreatic IL-17-producing Th17 and γδ-T cells in mice with ceruletide-induced pancreatitis.
Article in Basic & clinical pharmacology & toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 7 citations in OpenAlex.
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Thymic Bmi-1 hampers γδT17 generation and its derived RORγt-IL-17A signaling to delay cardiac aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning.International journal of molecular sciences · 2023Article
- A new method for the treatment of myocardial ischemia-reperfusion injury based on γδT cell-mediated immune response.Frontiers in cardiovascular medicine · 2023Article
- Integrative proteomics, phosphoproteomics and acetylation proteomics analyses of acute pancreatitis in rats.International journal of medical sciences · 2023Article
- RORγt inhibitor SR1001 alleviates acute pancreatitis by suppressing pancreatic IL-17-producing Th17 and γδ-T cells in mice with ceruletide-induced pancreatitis.Basic & clinical pharmacology & toxicology · 2021Article
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6 authors at 1 institution in 1 country.
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Abstract
The management of acute pancreatitis (AP) remains a challenge to clinicians worldwide for limited effective interventions. Retinoid orphan receptor gamma t (RORγt) is a therapeutic target for several diseases; however, it is unclear whether inhibiting RORγt can ameliorate AP. The relative expression of RORγt, IL-17 and IL-23 in the peripheral blood mononuclear cells of AP patients was measured by RT-PCR. An AP mouse model was induced by ceruletide, and SR1001 was injected before ceruletide administration. RORγt+ cells, T helper 17 cells (Th17), regulatory T cells (Tregs) and γδ T cells were assessed in the pancreas and spleen by flow cytometry. Higher RORγt expression in patients indicated the potential role of RORγt in AP progression. Analyses of the IL-17/IL-23 axis confirmed its role. SR1001 significantly alleviated AP histologically in the mouse model. Serum levels of amylase, IL-6, TNFalpha, IL-17 and IL-23 decreased upon SR1001 treatment. SR1001 selectively decreased the number of RORγt+, Th17, Tregs and γδ T cells in the pancreas but not the spleen. Collectively, these results showed that SR1001 exerted therapeutic effects on AP by suppressing IL-17-secreting Th17 and γδ T cells in the pancreas. Thus, SR1001 may be a promising drug for the treatment of AP in the clinic.
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