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Main Authors: Zhu, Junwen, Hao, Yongkang, Zhang, Fenghua, Gao, Xiaxia, Wang, Houpeng, Yu, Liqun, Wang, Xiaosi, Sun, Yonghua
Format: Artículo científico
Language:en
Published: Journal of genetics and genomics = Yi chuan xue bao 2026
Online Access:https://pubmed.ncbi.nlm.nih.gov/41780749/
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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/