IFNh and IRF9 influence the transcription of MHCII mediated by IFNγ to maintain immune balance in sea perch lateolabrax japonicus

• Published in: Fish & shellfish immunology 2024-10, Vol.153, p.109857, Article 109857
• Main Authors: Lu, Xiaobing, Hu, Zhe, Qin, Ziling, Huang, Hao, Yang, Taoran, Yi, Meisheng, Jia, Kuntong
• Format: Article
• Language: English
• Subjects: Animals; CIITA; Fish Proteins - genetics; Fish Proteins - immunology; Gene Expression Profiling - veterinary; Gene Expression Regulation - immunology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; IFNh; IFNγ; Immunity, Innate - genetics; Interferon-gamma - genetics; Interferon-gamma - immunology; Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics; Interferon-Stimulated Gene Factor 3, gamma Subunit - immunology; IRF9; Major histocompatibility complex class II; Nuclear Proteins; Trans-Activators
• ISSN: 1050-4648; 1095-9947; 1095-9947
• DOI: 10.1016/j.fsi.2024.109857

The major histocompatibility complex class II (MHCII) molecules are crucial elements of the adaptive immune system, essential for orchestrating immune responses against foreign pathogens. However, excessive expression of MHCII can disrupt normal physiological functions. Therefore, the host employs various mechanisms to regulate MHCII expression and maintain immune homeostasis. Despite this importance, limited studies have explored the negative regulation of MHCII transcription in bony fish. In this study, we found that interferon h (IFNh), a subtype of type I IFN in sea perch Lateolabrax japonicus, could inhibit the activation of IFNγ induced-MHCII expression by modulating the transcription of the class II major histocompatibility complex transactivator (CIITA). Transcriptome analysis revealed 57 up-regulated and 69 down-regulated genes in cells treated with both IFNγ and IFNh compared to those treated with IFNγ alone. To maintain cellular homeostasis, interferon regulatory factor 9 (IRF9) was up-regulated following IFNγ stimulation, thereby preventing MHCII overexpression. Mechanistically, IRF9 bound to the CIITA promoter and suppressed its expression activated by IRF1. Furthermore, IRF9 inhibited the promoter activity of both MHCII-α and MHCII-β induced by CIITA. Our findings highlight the roles of IFNh and IRF9 as suppressors regulating MHCII expression at different hierarchical levels. This study provides insights into the intricate regulation of antigen presentation and the foundation for further exploration of the interaction mechanisms between aquatic virus and fish. •IFNh suppresses MHCII expression induced by IFNγ.•IFNγ promotes IRF9 expression.•IRF9 inhibits MHCII expression induced by IFNγ through blocking IRF1 and CIITA function.