IL-9 and Blimp-1 protects the transcriptional identity of group 2 innate lymphocytes in allergic asthma

Although ILC2s are activated by the tissue alarmins IL-33 and IL-25, these signals do not intrinsically enforce type 2 identity, and the mechanisms that maintain type 2 cytokine expression remain unclear. Here we show that allergen-induced IL-33 and IL-25 rapidly induce IL-9, which in turn upregulates the transcriptional repressor Blimp-1 in ILC2s.

Blimp-1 sustains type 2 immunity by directly repressing type 1 inflammatory programs, including expression of IFNg and TNF. Deletion of Blimp-1 in ILC2s increased type 1 cytokine production and reduced IL-5 and IL-13 expression, eosinophil recruitment, and mucus production in the lung. In contrast, IL-9 expression was enhanced in the absence of Blimp-1, leading to increased mast cell recruitment.