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

## TL;DR

This study reveals how IL-9 and Blimp-1 help maintain the function of immune cells involved in allergic asthma.

## Contribution

The study identifies a novel mechanism by which IL-9 and Blimp-1 preserve the type 2 identity of innate lymphoid cells.

## Key findings

- IL-9 is rapidly induced by allergen-driven alarmins and upregulates Blimp-1 in ILC2s.
- Blimp-1 represses type 1 inflammation and promotes type 2 cytokine production in ILC2s.
- Deleting Blimp-1 in ILC2s reduces type 2 inflammation and allergic asthma symptoms.

## Abstract

Allergic asthma is driven by type 2 immune cells including type 2 innate lymphoid cells (ILC2s). ILC2s respond to the tissue alarmins IL-33 and IL-25, however these signals do not uniquely promote type 2 inflammation, and the factors that maintain ILC2s ability to produce type 2 cytokines are not known. Here, we show that allergen-driven tissue alarmins IL-33 and IL-25 rapidly induce IL-9, which directly upregulates the transcriptional repressor Blimp-1 through an autocrine/paracrine mechanism. Blimp-1 promotes type 2 responses by directly repressing type 1 inflammation including the cytokines IFNγ and TNF. Deletion of Blimp-1 in ILC2s increases type 1 cytokines and concomitantly reduces type 2 cytokines, ameliorating mucus production and airway inflammation in response to allergens. Thus, Blimp-1 maintains the type 2 transcriptional identity of ILC2s in response to inflammation, driving type 2 immunity and allergic asthma.