Rapid and functional intestinal regeneration after full-organ transection in zebrafish larvae is regulated by opposing effects of IL-22 and IL-26

ABSTRACT: The intestinal epithelium is among the most regenerative tissues, continuously renewing and repairing after damage. Severe injuries that disrupt all tissue layers, however, pose a distinct challenge, requiring restoration of the epithelium together with its surrounding tissues. Whether and how a vertebrate intestine can restore architecture and function after complete loss of gut continuity remains unknown. Here, we establish a larval zebrafish model of severe intestinal injury, in which full-organ transection disrupts all gut tissue layers. Following injury, the intestine rapidly reattaches, restores lumen continuity, and resumes food transit. This repair process is accompanied by mesenchymal remodeling and restoration of muscle continuity, and is promoted by transient epithelial proliferation. Injury induces a sox17-expressing epithelial progenitor-like state, with localized re-expression of this embryonic gut marker at the wound site. Injury also triggers transient neutrophil and macrophage recruitment to the wound site and broadens the range of epithelial cell types that express il22. STAT3 signaling is required for timely epithelial reattachment and injury-induced proliferation. Loss of IL-22 blunts early repair-associated responses, impairs reattachment, reduces proliferation, and limits lumen restoration. In contrast, loss of IL-26 enhances early epithelial repair programs, accelerates gap closure, and elevates proliferation in a mitosis-dependent manner. Together, these findings establish zebrafish larvae as a tractable vertebrate model for full-organ intestinal regeneration and identify IL-22 and IL-26 as opposing regulators of STAT3-associated repair

ORGANISM(S): Danio rerio

PROVIDER: GSE338160 | GEO | 2026/07/14

REPOSITORIES: GEO