Interleukin 9 fate reporter reveals induction of innate IL-9 response in lung inflammation

Interleukin 9 (IL-9) is a cytokine implicated in lung inflammation, but its cellular origin and function remain unclear. Here we describe a reporter mouse strain designed to fate map cells that have activated IL-9. We show that during papain-induced lung inflammation IL-9 production was largely restricted to innate lymphoid cells (ILC). IL-9 production by ILC was dependent on IL-2 from adaptive immune cells and was rapidly lost in favor of other cytokines, such as IL-13 and IL-5. Blockade of IL-9 production via neutralizing antibodies substantially reduced IL-13 and IL-5, suggesting that ILC provide the missing link between the well-established functions of IL-9 on the regulation of T(H)2 cytokines and responses.