Chronic pancreatitis (CP) is a progressive inflammatory disorder with no effective treatment, which underscores the urgent need for novel therapeutic strategies. In this study, single-cell sequencing data retrieved from the Gene Expression Omnibus (GEO) database revealed that Prkcq and IL-4 were highly induced in group 2 innate lymphoid cells (ILC2s), while Mitf and Tgm2 were highly expressed in tissue-resident macrophages (TRMs). A mouse model of CP was established using dibutyltin dichloride (DBTC), and pathological evaluations via H&E, Masson, and Sirius Red staining confirmed typical features of CP, including acinar atrophy, inflammatory cell infiltration, and increased fibrosis. Notably, the numbers of ILC2s and TRMs in pancreatic tissues were significantly elevated in DBTC-treated mice. Functional experiments showed that the Prkcq knockdown in ILC2s suppressed the expression of IL-4, IL-5 and IL-13, while in TRMs, the transcription factor Mitf upregulated Tgm2 expression. In CP mice, Prkcq knockdown reduced TRM abundance, ultimately alleviating pancreatic fibrosis. Collectively, this study identifies Prkcq as a key regulator of CP by modulating TRM populations.
Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL 4 ) in mice. ATT treatment markedly reduced the count of neutrophils in the liver, as well as macrophages in both the liver and spleen. Additionally, the frequencies of Th2 and Th17 cells were significantly lowered, while Th1 cells frequency and the Th1/Th2 index were notably increased. The frequency of ILC2 cells, correlated with ST2 and IL-33 expression levels, was also significantly lowered. Consistently, ATT inhibited NLRP3 inflammasome activation, which was positively associated with AST and ALT levels, and with the count of Neutrophils, macrophages, and ILC2 cells, but negatively correlated with Th1frequeny. Furthermore, liver fibrosis severity showed a significant positive correlation with neutrophil and Th17 cell counts in the liver, and a negative correlation with Th1 cell count and the Th1/Th2 index. Therefore, ATT alleviated CCL 4 -induced mice liver fibrosis through NLRP3 inflammasome inhibition and immunomodulation.
危险品化学品经营许可证（带存储）