iScience (Aug 2025)

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

DOI
https://doi.org/10.1016/j.isci.2025.113144
Journal volume & issue
Vol. 28, no. 8
p. 113144

Abstract

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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.

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