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<p>Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c<sup>+</sup> DCs and CD4<sup>+</sup> T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2<sup>+</sup> cDC2s and CCR7<sup>+</sup> DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2<sup>+</sup> cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.</p>

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Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月22日

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  • Peter C. Cook,
  • Sheila L. Brown,
  • Emma L. Houlder,
  • Julio Furlong-Silva,
  • Daniel P. Conn,
  • Stefano A. P. Colombo,
  • Syed Baker,
  • Freya R. Svedberg,
  • Gareth Howell,
  • Margherita Bertuzzi,
  • Louis Boon,
  • Joanne E. Konkel,
  • Christopher R. Thornton,
  • Judith E. Allen,
  • Andrew S. MacDonald

摘要

Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c+ DCs and CD4+ T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+ cDC2s and CCR7+ DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2+ cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.