Conserved functional features of natural killer cell subsets in chicken, human, and murine immune systems
Seung Je Woo,
Jaeryeong Kim,
Hong Jo Lee,
Kyung Youn Lee,
Kyung Je Park,
Jin-Kyoo Kim,
Jin Lee Kim,
Byung Chul Park,
Minseok Seo,
Jae Yong Han
Affiliations
Seung Je Woo
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
Jaeryeong Kim
Department of Computer and Information Science, Korea University, Sejong, Republic of Korea
Hong Jo Lee
Division of Animal Science, University of Missouri, Columbia, MO, USA
Kyung Youn Lee
Avinnogen Co., Ltd., Seoul 08826, Republic of Korea
Kyung Je Park
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
Jin-Kyoo Kim
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of International Agricultural Technology & Institute of Green Bioscience and Technology, Seoul National University, Pyeongchang, Republic of Korea
Jin Lee Kim
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
Byung Chul Park
Department of International Agricultural Technology & Institute of Green Bioscience and Technology, Seoul National University, Pyeongchang, Republic of Korea
Minseok Seo
Department of Computer and Information Science, Korea University, Sejong, Republic of Korea; Corresponding author
Jae Yong Han
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Avinnogen Co., Ltd., Seoul 08826, Republic of Korea; Corresponding author
Summary: Immunological conservation across species is crucial for comparative biology. While Natural killer (NK) cells' functions are conserved in humans and mice at the single-cell level, they remain unexplored in chickens due to technical limitations. Single-cell RNA sequencing in a recombination-activating gene 1-deficient (RAG1−/−) chicken model revealed two NK cell subpopulations (NK-1 and -2) in chickens, analogous to those in humans and mice. Cross-species analysis revealed that most genes exhibited distinct expression patterns within NK subsets, reflecting evolutionary divergence, though functional genes were conserved across chicken, humans, and mice. NK-1 cells exhibited conserved cytotoxic functions through immunological synapses and activated signaling pathways, while NK-2 cells exhibited conserved immune-regulatory functions via cytokine production. Transcription factors related to NK cells' terminal and early maturation were upregulated in NK-1 and NK-2 cells, respectively. These findings highlight evolutionarily conserved immune mechanisms, establishing chickens as potential avian models for translational research in developing treatments against infectious diseases.