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bioRxiv · 10.64898/2025.12.02.691763

Il33 expressing cDC2s promote expansion of ILC2s and eosinophilia in fungal airway inflammation in male mice

Graf, L.-M.·Radtke, D.·Ruhl, A.·Castiglione, K.·Wirtz, S.·Krappmann, S.·Schraml, B.·Voehringer, D.
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Abstract

Eosinophilic allergic asthma is often associated with fungal sensitization and represents the dominant form of asthma in adolescents. The mechanisms by which lung eosinophilia is regulated in this context are incompletely understood. Here, we demonstrate that type 2 innate lymphoid cells (ILC2s) are generally required in addition to Th2 cells for Aspergillus fumigatus-elicited eosinophilic lung inflammation in mice and this effect was independent of ILC2-derived IL-5. Surprisingly, expansion of ILC2s in male mice was ST2-independent, but required expression of Il33 in cDC2s induced by Th2-derived IL-4/13. This IL-33-plus IL-4-regulated transcriptional module in cDC2s included expression of factors associated with activation of ILC2s and was restricted to CCR7+ cDC2s in the inflamed lung. Our findings uncovered a novel intimate cross-talk between IL-33+ cDC2s, ILC2s and Th2 cells to orchestrate eosinophilia in a sex-dependent manner upon A. fumigatus-induced allergic lung inflammation.

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Graf, L.-M., Radtke, D., Ruhl, A., Castiglione, K., Wirtz, S., Krappmann, S., Schraml, B., Voehringer, D.. 2025-12-04. Il33 expressing cDC2s promote expansion of ILC2s and eosinophilia in fungal airway inflammation in male mice. https://doi.org/10.64898/2025.12.02.691763

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