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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of genetics and genomics = Yi chuan xue bao
2026
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41780749/ |
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| _version_ | 1868266077001089026 |
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| author | Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua |
| author_facet | Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua |
| collection | PubMed - marine biology |
| contents | Engineering Tregs-mediated immune tolerance via foxp3a overexpression to evade allograft transplantation barriers in zebrafish. Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua In mammals, regulatory T cells (Tregs) are widely exploited to promote immune tolerance in organ transplantation. In zebrafish, although germline stem cell (GSC) or gonadal primordium transplantation into immunodeficient hosts can accelerate gamete production, maintaining immunocompromised lines presents substantial practical challenges. To overcome this limitation, this study generates a Tg(CMV:foxp3a) zebrafish line through systemic overexpression of Forkhead box P3a (Foxp3a), the lineage-defining transcription factor of Tregs. Transcriptomic and in situ hybridization analysis reveal downregulation of the Treg negative regulator cd127 and upregulation of multiple immunosuppressive factors in the head kidney and thymus. Single-cell RNA sequencing further demonstrates a reduction in effector T and B cell populations, accompanied by an increase in quiescent T cells exhibiting resting Treg-like features. Importantly, using Tg(CMV:foxp3a) fish as hosts for subcutaneous gonadal primordium transplantation and intraperitoneal GSC transplantation markedly accelerates germ cell maturation and enables efficient establishment of stable transgenic lines. Post-transplantation analysis indicates delayed and attenuated immune activation, enhanced graft survival, and rapid induction of immunosuppressive states. Together, foxp3a overexpression reshapes the immune landscape to confer immune tolerance, providing a practical Tregs-based alternative to immunodeficient hosts for fish genome manipulation and transplantation. |
| format | Artículo científico |
| id | pubmed_41780749 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of genetics and genomics = Yi chuan xue bao |
| record_format | pubmed |
| spellingShingle | Engineering Tregs-mediated immune tolerance via foxp3a overexpression to evade allograft transplantation barriers in zebrafish. Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua Engineering Tregs-mediated immune tolerance via foxp3a overexpression to evade allograft transplantation barriers in zebrafish. Zhu, Junwen Hao, Yongkang Zhang, Fenghua Gao, Xiaxia Wang, Houpeng Yu, Liqun Wang, Xiaosi Sun, Yonghua In mammals, regulatory T cells (Tregs) are widely exploited to promote immune tolerance in organ transplantation. In zebrafish, although germline stem cell (GSC) or gonadal primordium transplantation into immunodeficient hosts can accelerate gamete production, maintaining immunocompromised lines presents substantial practical challenges. To overcome this limitation, this study generates a Tg(CMV:foxp3a) zebrafish line through systemic overexpression of Forkhead box P3a (Foxp3a), the lineage-defining transcription factor of Tregs. Transcriptomic and in situ hybridization analysis reveal downregulation of the Treg negative regulator cd127 and upregulation of multiple immunosuppressive factors in the head kidney and thymus. Single-cell RNA sequencing further demonstrates a reduction in effector T and B cell populations, accompanied by an increase in quiescent T cells exhibiting resting Treg-like features. Importantly, using Tg(CMV:foxp3a) fish as hosts for subcutaneous gonadal primordium transplantation and intraperitoneal GSC transplantation markedly accelerates germ cell maturation and enables efficient establishment of stable transgenic lines. Post-transplantation analysis indicates delayed and attenuated immune activation, enhanced graft survival, and rapid induction of immunosuppressive states. Together, foxp3a overexpression reshapes the immune landscape to confer immune tolerance, providing a practical Tregs-based alternative to immunodeficient hosts for fish genome manipulation and transplantation. |
| title | Engineering Tregs-mediated immune tolerance via foxp3a overexpression to evade allograft transplantation barriers in zebrafish. |
| url | https://pubmed.ncbi.nlm.nih.gov/41780749/ |