Mgl2<sup>+</sup>cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation
Abstract 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. We found that CD11c+DCs and CD4+T cells are essential for development of both type 2 and type 17 airway inflammation in mice when repeatedly exposed to inhaled spores. Single cell RNA-sequencing enabled the development of multi-parameter cytometry that identified allergic inflammation dramatically altered the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+cDC2s and CCR7+DCs) migrated to the dLNs. Targeted removal of several DC subsets revealed that only Mgl2+cDC2 depletion dramatically reduced type 2, but not type 17, anti-fungal allergic airway inflammation. These data highlight distinct DC subsets are potential therapeutic targets for the treatment of pulmonary fungal disease..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 13. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cook, Peter C [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.11.24.568263 |
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| PPN (Katalog-ID): |
XBI041643054 |
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| 520 | |a Abstract 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. We found that CD11c+DCs and CD4+T cells are essential for development of both type 2 and type 17 airway inflammation in mice when repeatedly exposed to inhaled spores. Single cell RNA-sequencing enabled the development of multi-parameter cytometry that identified allergic inflammation dramatically altered the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2+cDC2s and CCR7+DCs) migrated to the dLNs. Targeted removal of several DC subsets revealed that only Mgl2+cDC2 depletion dramatically reduced type 2, but not type 17, anti-fungal allergic airway inflammation. These data highlight distinct DC subsets are potential therapeutic targets for the treatment of pulmonary fungal disease. | ||
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| 700 | 1 | |a Baker, Syed |4 aut | |
| 700 | 1 | |a Svedberg, Freya R. |4 aut | |
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| 700 | 1 | |a Konkel, Joanne E. |4 aut | |
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