Abstract

Background and Purpose Allergic rhinitis, a common chronic inflammatory condition characterized by T-cell imbalance and mast cell hyperactivity, had not been investigated for the role of Lyn kinase within mast cells and its effects on T helper cell differentiation. α-Linolenic acid (ALA), a dietary supplement, exerts anti-allergic and anti-inflammatory effects. This study investigated the function of Lyn kinase in mediating mast cell-promoted Th17 cell differentiation during ALA treatment for allergic rhinitis. Experimental Approach Behavioural symptoms, serum inflammatory factors, nasal pathological damage and splenic T cell differentiation were assessed in models of allergic rhinitis, using wild type and Cpa3-cre;Lyn fl/+ mice. Effects of ALA and mast cells on Th17 differentiation were evaluated in co-culture assays. Binding characteristics of ALA to Lyn were analysed via surface plasmon resonance, molecular docking and co-immunoprecipitation. Phosphorylation of Lyn and lipid raft assembly were investigated by immunofluorescence and western blot in vitro. Key Results ALA administration alleviated allergic rhinitis symptoms and inflammation, restored Th17/Treg balance and produced comparable therapeutic results in Cpa3-cre;Lyn fl/+ mice. In vitro, Th17 cell differentiation was increased by Ag/IgE-activated mast cells and this increase was inhibited by ALA. Functionally, ALA acted as a Lyn kinase inhibitor, blocking Ag/IgE-induced mast cell degranulation. By binding to Lyn, ALA disrupted the FcεRIβ-Lyn interaction and inhibited lipid raft assembly. Conclusion and Implications Lyn kinase in mast cells plays a critical role in the pathogenesis of allergic rhinitis. ALA represents a novel Lyn-targeting agent, restoring immune balance by modulating mast cell-promoted Th17 differentiation, highlighting its potential for allergic rhinitis treatment. Graphical The mechanism