The Poultry Genetics and Breeding Research Team revealed a new mechanism by which the GA-binding protein transcription complex (GABP) regulates the development of natural killer (NK) cells in animals in collaboration with partners. This finding provides new insights into the regulation of immune cell development and disease-resistant breeding in animals. The related research findings were published in Science Bulletin.

As one of the three major types of lymphocytes, Natural killer (NK) cells are cytotoxic innate lymphocytes crucial for rapid immune responses against pathogens and tumors. Natural killer cells play a key role in killing pathogen-infected cells. NK cells can rapidly respond to biological processes such as pathogen invasion by secreting cytokines and exerting cytotoxic effects, making them a crucial pathway for the body to resist pathogen infections.

The development and maturation of NK cells are regulated by various transcription factors. This study found that GABP gene deficiency led to a significant reduction in the proportion and number of NK cells in peripheral lymphoid tissues, while their proportion and number increased in the bone marrow. The study also revealed that GABP-deficient NK cells exhibited weakened cytotoxicity and reduced secretion of interferons and other factors. Combined transcriptome sequencing and chromatin immunoprecipitation analyses showed that GABP deficiency caused dysregulation in the expression of several key genes involved in NK cell development and regulation. Further analysis indicated that the inactivation of the GABP tetramer could directly regulate the expression of multiple critical NK cell development-related genes, thereby suppressing NK cell function and animal disease resistance. This study demonstrates that GABP regulates the differentiation and maturation of NK cells, providing new genetic resources for disease-resistant breeding in animals.

Professor Li Qinghe from the Institute of Animal Science of CAAS, Yu Shuyang from China Agricultural University, and Xu Jingyu from Guizhou Medical University served as co-corresponding authors of the paper. The study got support from project of the National Livestock and Poultry Breeding Science Center of CAAS.

Article link: https://www.sciencedirect.com/science/article/abs/pii/S2095927325006139?via%3Dihub