KQS1 peptide represses food allergic responses via Dectin-1-dependent H3K27me3 epigenetic silencing of Fcer1a in mast cells

Abstract

Background KQS1 is a bioactive peptide derived from red bean that has shown anti-allergic activity in preclinical models; however, its effects on mast-cell responses and the epigenetic mechanisms potentially involved remain incompletely defined. Objective To investigate whether preventive oral administration of KQS1 attenuates food-allergy-associated responses and its mechanism. Methods An OVA-induced murine food-allergy model was established with preventive oral gavage of KQS1. Systemic and intestinal allergic-associated outcomes and mast-cell activation were assessed. Primary mouse bone-marrow-derived mast cells and human cord-blood-derived mast cells were used for cellular and mechanistic studies. Pharmacological inhibition of EZH2 and genetic perturbation of KDM6B were used to examine the functional contribution of H3K27me3-related regulation. In vitro loss-of-function assays using Clec7a-deficient mast cells were implemented to dissect the requirement of Dectin-1 for KQS1-triggered H3K27me3 deposition at the Fcer1a locus, and PRC2-EZH2 recruitment to Fcer1a regulatory regions was characterized by ChIP-qPCR. Results Under the preventive dosing conditions tested, oral KQS1 attenuated selected systemic and intestinal manifestations of experimental food allergy and reduced mast-cell degranulation. KQS1 was associated with reduced chromatin accessibility and increased H3K27me3 enrichment at selected regulatory regions of the Fcer1a locus, accompanied by reduced Fcer1a transcription and FCER1A surface expression. Dectin-1 deficiency abolishes KQS1-driven H3K27me3 accumulation at Fcer1a , demonstrating Dectin-1 signaling is required for this epigenetic event; EZH2 recruitment to the Fcer1a promoter upon KQS1 treatment is strictly Dectin-1-dependent. Dectin-1 perturbation, EZH2 inhibition, or KDM6B overexpression partially attenuated these KQS1-associated molecular and functional changes. Selected molecular and functional responses were partially recapitulated in human primary mast cells. A single intraperitoneal KQS1 injection induces sustained H3K27me3 modification, repressed Fcer1a transcription and durable mast-cell functional suppression for at least 28 days in vivo ; this long-lived epigenetic reprogramming is cell-intrinsic, validated by peptide-washout and restimulation assays in purified primary mast cells. Conclusions Oral KQS1 attenuates experimental food-allergy-associated responses and mast-cell activation under preventive conditions by engaging Dectin-1 signaling, which directs PRC2-dependent H3K27me3 epigenetic silencing of Fcer1a in mast cells. The findings establish the linear causal cascade from Dectin-1-associated signaling to H3K27me3-mediated Fcer1a repression.

The authors' abstract, as published at the source. Frontiers in Immunology, 2026 · DOI ↗