HDAC1 and SATB1 positively regulate immune responses in chicken macrophages

TL;DR

This study shows that HDAC1 and SATB1 proteins help chicken immune cells fight infections, offering new ways to improve poultry health and disease resistance.

Contribution

The study reveals a novel synergistic mechanism of HDAC1 and SATB1 in regulating immune responses in chicken macrophages.

Findings

HDAC1 and SATB1 are up-regulated in chicken macrophages during immune stimulation.

Disruption of HDAC1 or SATB1 reduces the expression of key immune effectors like IFN-β and TNF-α.

HDAC1 and SATB1 are evolutionarily conserved and physically interact in chicken cells.

Abstract

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.

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