ArticleGenes and immunity2026
PRSS1 isoforms promote type 2 immune responses in IgG4-related disease.
Article in Genes and immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Trypsin is commonly used as an adjunctive therapeutic agent for chronic inflammatory and autoimmune diseases. This study investigated the impact of trypsinogen (PRSS1) variants on type 2 immune responses mediated by M2 macrophage polarization in immunoglobulin G4-related disease (IgG4-RD). Whole-exome sequencing of affected tissue samples from patients with IgG4-RD, including two cases of IgG4-related autoimmune pancreatitis and one case of Mikulicz disease, identified novel PRSS1 variants, namely p.Lys70Asn and p.Phe73Leu. Activation of M2 macrophages was observed in these affected tissues. By integrating single-cell RNA sequencing datasets with spatial transcriptomic analysis of pancreatic tissues from mutation-positive cases, we found that molecules produced by M2 macrophages, including TGF-β, may promote type 2 immune responses. In conclusion, novel PRSS1 variants may contribute to the pathogenesis of IgG4-RD by activating type 2 immune responses.
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Registered trials
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