CD103+ Dendritic Cells Control Th17 Cell Function in the Lung

• Aspergillus-germinated morphotypes induce IL-2 in lung CD103+ dendritic cells
• IL-2 production is dependent on the Ca2+-calcineurin-NFAT pathway
• Deletion of dendritic-cell-derived IL-2 leads to higher mortality upon infection
• Dendritic-cell-derived IL-2 regulates Th17 cell phenotype

SummaryTh17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103+ dendritic cells (DCs) would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem-cell-like population. Although several cell types may be affected by deficient IL-2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection.

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