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<p>Allergic asthma is driven by type 2 immune responses, including type 2 innate lymphoid cells (ILC2s). Although ILC2s are activated by the tissue alarmins interleukin (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 interferon-γ and tumor necrosis factor. 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. Together, these findings identify Blimp-1 as a key regulator of ILC2 transcriptional fidelity that stabilizes type 2 inflammation while constraining divergent inflammatory programs during allergic responses.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月24日

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  • Yibo Zheng,
  • Shilpi Giri,
  • Jinyi Zhang,
  • Yijia Chen,
  • Aaron Yang,
  • Sagar L. Kale,
  • Harshita Beeravolu,
  • Abbe Pannucci,
  • Anthony D. Marinov,
  • Jeremy S. Tilstra,
  • Kun He,
  • Arianna Creech,
  • Daniella M. Schwartz,
  • Rachel A. Gottschalk,
  • Nicolas Bouladoux,
  • Yasmine Belkaid,
  • Anthony R. Cillo,
  • Anuradha Ray,
  • Amanda C. Poholek

摘要

Allergic asthma is driven by type 2 immune responses, including type 2 innate lymphoid cells (ILC2s). Although ILC2s are activated by the tissue alarmins interleukin (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 interferon-γ and tumor necrosis factor. 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. Together, these findings identify Blimp-1 as a key regulator of ILC2 transcriptional fidelity that stabilizes type 2 inflammation while constraining divergent inflammatory programs during allergic responses.