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

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. ### Competing Interest Statement Individuals based at the Lydia Becker Institute received funding from GSK. These authors (P.C.C., S.L.B, E.L.H., F.R.S., A.S.M.) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The remaining authors declare no competing interests.