Blimp-1 protects the transcriptional identity of group 2 innate lymphocytes in lung inflammation [ATAC-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. Overall design: 2 female Blimp-1IL7RaCre and 2 female ControlIL7RaCre mice match with age were used. Whole lung was harvested and ILC2s were sorted from lung by the following markers: live, lineage-, CD90.2+, CD3-. After sorting, ~15,000 ILC2s cells from each sample were cultured in complete RPMI in 96-well plate with 20ng/mL IL-33 and 20ng/mL IL-25 for 72 hours. After 72 hours, ILC2s were collected passed down for sequencing.