| First Author | Forster PM | Year | 2026 |
| Journal | J Exp Med | Volume | 223 |
| Issue | 5 | PubMed ID | 41915169 |
| Mgi Jnum | J:385318 | Mgi Id | MGI:8318801 |
| Doi | 10.1084/jem.20250781 | Citation | Forster PM, et al. (2026) Blimp-1 integrates alarmin signals in ILC2s and drives proinflammatory functions required for type 2 immunity. J Exp Med 223(5) |
| abstractText | Type 2 immunity has evolved to protect against worms but becomes harmful when activated during allergic inflammation. Group 2 innate lymphoid cells (ILC2s) drive type 2 responses by rapidly secreting IL-5 and IL-13. The alarmins, IL-25, IL-33, and TSLP activate ILC2s and are linked to allergic diseases. However, how alarmins connect to the transcriptional networks driving type 2 effector functions remains elusive. Here, we performed RNA sequencing of ILC2s deficient in IL-25, IL-33, or TSLP pathway and identified the transcription factor Blimp-1 as an IL-33-regulated gene in ILC2s. While Blimp-1 was dispensable for ILC2 development, this transcription factor was required for type 2 cytokine production, driving eosinophilia or promoting worm expulsion. Blimp-1 deficiency resulted in reduced IRF4 expression, while Irf4-deficient ILC2s showed diminished Blimp-1 and IL-33 receptor expression, revealing a reciprocal Blimp-1-IRF4 circuit downstream of the IL-33 receptor. These findings expose the Blimp-1-IRF4 axis as an alarmin-regulated transcriptional network controlling ILC2 effector functions required for type 2 immunity. |
