Prkcq in ILC2 cells-enhanced the amounts of tissue-resident macrophages promotes pancreatic fibrosis in chronic pancreatitis.

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.