ArticleResearch square2025
IL-9 and Blimp-1 protects the transcriptional identity of group 2 innate lymphocytes in allergic asthma.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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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.
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