Exploring the Role of Acrylamide in Food Allergy via Dendritic Cell‐Dependent Th2 Immune Responses

ABSTRACT Acrylamide (AA), a prevalent food processing contaminant with recognized multi‐organ toxicity, has an unexplored immunomodulatory role in food allergy (FA). This study integrated in vivo and in vitro models to elucidate the mechanisms by which AA regulates immune responses during ovalbumin (OVA, egg ovalbumin)‐sensitized mice. In vivo experiments demonstrated that AA exposure significantly exacerbated allergic symptoms and inflammatory responses in sensitized mice, including diarrhea, weight loss, elevated levels of β‐Hex, MCP‐1, OVA‐specific IgE, IgG, and IgG1 antibodies, and Th2‐type cytokines (IL‐4, IL‐6, IL‐13), accompanied by suppression of the anti‐inflammatory cytokine IL‐10. Moreover, AA exhibited Th2‐skewing adjuvant activity while promoting Th17 differentiation, leading to Th2/Th17 imbalance. Mechanistic studies revealed that AA enhanced the antigen uptake capacity of dendritic cells (DCs) and promoted their activation. In the BMDC/T cell co‐culture system, AA promoted Th2 polarization, as indicated by an increased GATA3⁺/T‐bet⁺ ratio. Furthermore, AA synergized with OVA to induce inflammatory responses via activation of the TLR4/MyD88/NF‐κB signaling pathway, with significant upregulation of phosphorylated IκB‐α (P‐IκB‐α) and phosphorylated NF‐κB p65 (P‐NF‐κB p65) observed particularly in the high‐dose AA group. These findings established AA as a foodborne immunotoxin that primes allergic inflammatory susceptibility through DC‐dependent Th2/Th17 polarization, amplification of TLR4/NF‐κB signaling, and suppression of IL‐10 production. This study provides novel mechanistic insights into the immunoadjuvant effects of AA, offering crucial experimental evidence for developing preventive strategies against diet‐driven allergic diseases.