| First Author | Saini A | Year | 2026 |
| Journal | Nat Commun | Volume | 17 |
| Issue | 1 | PubMed ID | 41832176 |
| Mgi Jnum | J:385018 | Mgi Id | MGI:8328866 |
| Doi | 10.1038/s41467-026-70636-4 | Citation | Saini A, et al. (2026) Cell type-specific enhancers regulate IL-22 expression in innate and adaptive type 3 lymphoid cells. Nat Commun 17(1) |
| abstractText | IL-22, a signature cytokine for type 3 lymphoid cells, including T helper 17/22 (Th17/22) and type 3 innate lymphoid cells (ILC3), mediates epithelial homeostasis and protective pathogen responses in barrier tissues. Upon dysregulation, IL-22 can drive chronic inflammatory diseases, yet little is known about transcriptional elements modulating its expression. Here, we identify two enhancers, E22-1 and E22-2, with distinct capacities for regulating Il22 expression in type 3 lymphoid cells. Both enhancers are necessary for protection from Citrobacter rodentium infection and for the onset of IL-22-mediated psoriasis. E22-2 is specifically required for IL-22 expression in ILC3s, while E22-1 functions in both Th17/22 and ILC3. The ILC3 specificity of E22-2 is attributed to the presence of multiple Runx3 sites and the lack of a functional RORgammat motif. We conclude that Th17/22 and ILC3 cells use distinct cis-elements to differentially regulate IL-22 expression, while orchestrating homeostatic protection and pathogen defense in barrier tissues. |
