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<p>Enzymatic crosslinking has emerged as an effective strategy to reduce allergenicity, but the underlying immunological mechanisms involved remain largely unknown. Here we developed a hypoallergenic house dust mite (HDM) product, termed Tyr-HDM, by tyrosinase/caffeic acid–mediated crosslinking combined with galactomannan conjugation. Compared with control HDM, Tyr-HDM exhibited significantly reduced allergenic activity in a murine model of allergic asthma, as evidenced by attenuated airway inflammation and diminished T helper 2 (Th2) responses, including reduced IL-4, IL-5 and IL-13 production, accompanied by a notable increase in regulatory T (Treg) cells. Further mechanistic analysis revealed that Tyr-HDM modulated the Treg/Th2 balance through activation of the AMPKα−RALDH2 signaling axis specifically within type 1 conventional dendritic cells (cDC1s). Importantly, pharmacological inhibition of AMPK activity abolished the Tyr-HDM–induced Treg/Th2 reprogramming and the associated attenuation of allergic inflammation. In contrast, AMPK activation in cDC1s alleviated HDM−induced allergic inflammation. Notably, Tyr-HDM exerted both protective and therapeutic efficacy in HDM-driven allergic airway inflammation. Collectively, these findings demonstrate that enzymatically crosslinked HDM possesses reduced allergenic activity and distinct immunomodulatory properties and identify the AMPKα−RALDH2 axis in cDC1s as a key pathway linking allergen modification to immune regulation in allergic airway inflammation.</p>

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Enzyme−Crosslinked House Dust Mite Exhibits Reduced Allergenic Activity by Reprogramming the AMPKα−RALDH2 Axis in Type 1 Dendritic Cells

  • 期刊论文

  • 发表日期：

    2026年4月13日

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  • Tingting Zheng,
  • Ishfaq Ahmed,
  • Jiaqi Deng,
  • Jiawen Shang,
  • Yutong Yang,
  • Wanjuan Zhong,
  • Luwen Zhang,
  • Weibin Jiang,
  • Yangjie Zeng,
  • Caimei Song,
  • Yanyan Wang,
  • Suidong Ouyang,
  • Meng Yang,
  • Xinguang Liu,
  • Lei Wu,
  • Jinlyu Sun,
  • Gonghua Huang

摘要

Enzymatic crosslinking has emerged as an effective strategy to reduce allergenicity, but the underlying immunological mechanisms involved remain largely unknown. Here we developed a hypoallergenic house dust mite (HDM) product, termed Tyr-HDM, by tyrosinase/caffeic acid–mediated crosslinking combined with galactomannan conjugation. Compared with control HDM, Tyr-HDM exhibited significantly reduced allergenic activity in a murine model of allergic asthma, as evidenced by attenuated airway inflammation and diminished T helper 2 (Th2) responses, including reduced IL-4, IL-5 and IL-13 production, accompanied by a notable increase in regulatory T (Treg) cells. Further mechanistic analysis revealed that Tyr-HDM modulated the Treg/Th2 balance through activation of the AMPKα−RALDH2 signaling axis specifically within type 1 conventional dendritic cells (cDC1s). Importantly, pharmacological inhibition of AMPK activity abolished the Tyr-HDM–induced Treg/Th2 reprogramming and the associated attenuation of allergic inflammation. In contrast, AMPK activation in cDC1s alleviated HDM−induced allergic inflammation. Notably, Tyr-HDM exerted both protective and therapeutic efficacy in HDM-driven allergic airway inflammation. Collectively, these findings demonstrate that enzymatically crosslinked HDM possesses reduced allergenic activity and distinct immunomodulatory properties and identify the AMPKα−RALDH2 axis in cDC1s as a key pathway linking allergen modification to immune regulation in allergic airway inflammation.