Year: 2025
Type: article
Abstract: Intestinal inflammation is a common challenge in intensive aquaculture, yet its pathogenesis remains unclear. While interleukin 22 (IL-22) is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates, its roles in fish are not well understood. This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis. Results revealed that Pelteobagrus fulvidraco IL-22 (Pf_IL-22) was abundantly expressed in mucosal tissues, with the highest levels in the gill and intestine. Hypoxia induced pronounced intestinal injury, characterized by loosening of the lamina propria and extensive vacuolization, while activating hypoxia-inducible factor (HIF) signaling and markedly up-regulating IL-22 expression. IL-22 levels peaked at 24 h post-hypoxia, suggesting a role in early immune responses. Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators, including IL-1β and tumor necrosis factor α (TNF-α), in primary intestinal epithelial cells, indicating a dual regulatory function in balancing protection and inflammation. Mechanistic analyses revealed that HIF-1α directly interacted with a hypoxia response element within the IL-22 promoter to drive transcription, as confirmed by dual-luciferase assays, electrophoretic mobility-shift assays, and HIF-1α knockdown. Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways, demonstrating its role in shaping downstream immune responses. These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation, providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.
Source: 动物学研究
Authors: Huan Heng-Qing, 南京师范大学海洋科学与工程学院, 江苏省特色水产育种与绿色高效养殖技术工程研究中心, 海-陆环境演变与生态建设实验室, 江苏 南京 210023, 中国, Ding Yu-Bing, Qian Zi-Ang, Ji Jie, Ning Xian-Hui, Yin Shao-Wu, Zhang Kai, 江苏省海洋生物产业技术协同创新中心, 江苏 连云港 222005, 中国
Institution: Nanjing Normal University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
Award: G4658705986
OpenAlex ID: W4414625339