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Peer-reviewedCC BY-NC-ND 4.0Poultry Science

Thymic single-cell RNA sequencing reveals the immunosuppressive microenvironment in chicken model simulating vertical transmission of recombinant ALV

1 more authors
  1. 1College of Animal Science, Fujian Agricultural and Forestry University, Fuzhou, 350002, China
  2. 2Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agricultural and Forestry University, Fuzhou, 350002, China

Abstract

Avian leukosis virus (ALV) induces immunosuppression and tumorigenesis. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptional dynamics of thymic immune cells in specific-pathogen-free (SPF) chickens, which were intra-embryonic infected with the naturally recombinant ALV-FJ15TH0, at 1-day-old (d), 28d, and 56d post-hatch. Using subgroup-specific marker genes and cell state analysis, we identified six T-cell clusters, two B-cell clusters, and a macrophage cell cluster. Differential gene analysis revealed that ALV infection resulted in a significant enrichment of downregulated genes across all immune cell subsets at 28d. Functional enrichment analysis indicated that ALV infection activated the FoxO immunosuppressive pathway, PI3K pathway, MAPK pathway (CD4+CD8+ T cells and M2 macrophages at 1d), multicellular synergistic regulation of the cancer pathway (CD4+CD8+ T cells, M2 macrophages, and Cytotoxic T cells at 28d), and ErbB signaling pathway, Notch signaling pathway (CD4+CD8+ T cells and M2 macrophages at 56d). Cell-cell communication analysis revealed that ALV infection induced the strongest predicted communication via the PPIA-BSG axis at 28 d. Analysis further inferred that CD147 (BSG) was associated with multiple signaling pathways, including MAPK/ERK and PI3K/AKT, which may contribute to the immunosuppressive microenvironment. BCL11B, SP3, and EP300 were identified as potential regulatory components with subset-specific associations with JUN, BRAF, and MYB, potentially involving the MAPK, PI3K/AKT, and FoxO signaling pathways. This study reveals the dynamic evolution of the thymic immune microenvironment following ALV-FJ15TH0 infection, providing a resource for understanding the molecular mechanisms underlying ALV-induced immunosuppression and offering a foundation for future investigation of its potential relationship with tumorigenesis.

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BibTeX
@article{zhang2026thymic,
  title = {{Thymic single-cell RNA sequencing reveals the immunosuppressive microenvironment in chicken model simulating vertical transmission of recombinant ALV}},
  author = {Danyang Zhang and Yuxin Pan and Zhaoting Zhong and Qingxin Gu and Wan Qiu and Nan Chen and Kuiyang Meng and Zuxin Gong and Yukun Zeng and Jinrong Zhao and Ping Liu and Yijian Wu and Xiaoping Wu},
  journal = {Poultry Science},
  year = {2026},
  month = oct,
  doi = {10.1016/j.psj.2026.108033},
  url = {https://doi.org/10.1016/j.psj.2026.108033},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Thymic single-cell RNA sequencing reveals the immunosuppressive microenvironment in chicken model simulating vertical transmission of recombinant ALV
AU  - Danyang Zhang
AU  - Yuxin Pan
AU  - Zhaoting Zhong
AU  - Qingxin Gu
AU  - Wan Qiu
AU  - Nan Chen
AU  - Kuiyang Meng
AU  - Zuxin Gong
AU  - Yukun Zeng
AU  - Jinrong Zhao
AU  - Ping Liu
AU  - Yijian Wu
AU  - Xiaoping Wu
PY  - 2026
DA  - 2026/10/23
JO  - Poultry Science
DO  - 10.1016/j.psj.2026.108033
UR  - https://doi.org/10.1016/j.psj.2026.108033
AB  - Avian leukosis virus (ALV) induces immunosuppression and tumorigenesis. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptional dynamics of thymic immune cells in specific-pathogen-free (SPF) chickens, which were intra-embryonic infected with the naturally recombinant ALV-FJ15TH0, at 1-day-old (d), 28d, and 56d post-hatch. Using subgroup-specific marker genes and cell state analysis, we identified six T-cell clusters, two B-cell clusters, and a macrophage cell cluster. Differential gene analysis revealed that ALV infection resulted in a significant enrichment of downregulated genes across all immune cell subsets at 28d. Functional enrichment analysis indicated that ALV infection activated the FoxO immunosuppressive pathway, PI3K pathway, MAPK pathway (CD4+CD8+ T cells and M2 macrophages at 1d), multicellular synergistic regulation of the cancer pathway (CD4+CD8+ T cells, M2 macrophages, and Cytotoxic T cells at 28d), and ErbB signaling pathway, Notch signaling pathway (CD4+CD8+ T cells and M2 macrophages at 56d). Cell-cell communication analysis revealed that ALV infection induced the strongest predicted communication via the PPIA-BSG axis at 28 d. Analysis further inferred that CD147 (BSG) was associated with multiple signaling pathways, including MAPK/ERK and PI3K/AKT, which may contribute to the immunosuppressive microenvironment. BCL11B, SP3, and EP300 were identified as potential regulatory components with subset-specific associations with JUN, BRAF, and MYB, potentially involving the MAPK, PI3K/AKT, and FoxO signaling pathways. This study reveals the dynamic evolution of the thymic immune microenvironment following ALV-FJ15TH0 infection, providing a resource for understanding the molecular mechanisms underlying ALV-induced immunosuppression and offering a foundation for future investigation of its potential relationship with tumorigenesis.
SN  - 0032-5791
SN  - 1525-3171
ER  -