IL-9 and Blimp-1 protect the transcriptional identity of group 2 innate lymphocytes in allergic asthma [RNA-seq]

Type 2 inflammation in the lung underlies allergic asthma and promotes tumor metastasis. Type 2 innate lymphoid cells (ILC2s) respond to tissue damage signals including IL-33 and IL-25 and are implicated in type 2 inflammatory diseases of the lung, but the factors that maintain ILC2s ability to produce type 2 cytokines are not known. We show Blimp-1 is a key transcriptional repressor of type 1 genes induced by the type 2 cytokine IL-9 in ILC2s in response to tissue damage signals. Loss of Blimp-1 in ILC2s altered inflammation in response to allergens, but also limited metastatic melanoma in the lung by limiting type 2 cytokines in favor of type I cytokines including IFNg and TNF. Thus, Blimp-1 protects the type 2 identity of ILC2s during lung inflammatory diseases.