Allergen-Induced IL-6 Regulates IL-9/IL-17A Balance in CD4+ T Cells in Allergic Airway Inflammation
IL-9–secreting Th9 cells have been considered to play a pivotal role in the pathogenesis of atopic diseases. To what extent IL-9–producing cells are induced or regulated by sensitization with naturally occurring allergens is not yet clear. Naturally occurring allergens are capable of inducing IL-6 production in dendritic cells (DCs). Whether allergen-induced IL-6 supports a Th9 subtype by increasing IL-9 production, as observed in in vitro studies, or rather favors Th17 differentiation is not finally resolved. Therefore, in the present study we have investigated the impact of IL-6 on the Th9/Th17 balance depending on the predominant cytokine milieu and, additionally, in vivo using a DC-driven murine asthma model. In vitro, IL-6 increases Th9 cells under strong IL-4 and TGF-β activation, whereas under moderate IL-4 and TGF-β activation the presence of IL-6 shifts naive CD4 + cells to Th17 cells. To induce allergic airway inflammation, OVA-pulsed DCs from IL-6–deficient or wild-type donors were adoptively transferred into BALB/c mice. Recipients receiving IL-6–producing wild-type DCs showed a significant decrease of Th9- and IL-4–producing Th2 cells but an increase of Th17 cells in lung tissue in comparison with recipients sensitized with IL-6–deficient DCs. Our data suggest that the IL-6–mediated reduction of Th2-related IL-4 leads to a decline of the Th9 immune response and allows Th17 differentiation.
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