HDAC1 and SATB1 positively regulate immune responses in chicken macrophages.

The avian immune system constitutes the primary barrier against pathogen invasion, and its regulatory efficiency directly determines animal health, productive performance, and food safety. Elucidating the molecular and cellular networks that maintain immune homeostasis in poultry has therefore become a pivotal entry point for improving disease prevention and achieving environmentally sustainable production. Histone deacetylase 1 (HDAC1) and special AT-rich sequence-binding protein 1 (SATB1) are reported modulators of immunity in some species such as mammals, yet their roles in avian species remain undefined. Here, we employed chicken macrophages (HD11) stimulated with lipopolysaccharide (LPS) to establish an in vitro immune-response model. Both HDAC1 and SATB1 were markedly activated and up-regulated upon LPS challenge. Using cell transfection and CRISPR/Cas9 genome editing, we generated HD11 cell lines with stable disruption of either HDAC1 or SATB1. In these modified cells, the LPS-induced elevation of key immune effectors-including IFN-β, IRF7, STAT1, TNF-α, and IFIH1 was significantly attenuated. Amino-acid sequence alignment, protein complex prediction, and co-immunoprecipitation further suggest that HDAC1 and SATB1 are evolutionarily conserved and physically interact. Collectively, our study uncovers a novel mechanism by which HDAC1 and SATB1 act synergistically to positively regulate immune responses in chicken macrophages. These findings not only provide new theoretical insights into avian immune regulation but also establishes a molecular foundation for the development of next-generation immune enhancers and breeding strategies that enhance disease resistance.