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Recombinant FOXN1 fusion protein increases T cell generation in aged mice

BACKGROUND: Although the thymus continues to export T cells throughout life, it undergoes a profound involution/atrophy with age, resulting in decreased numbers of T cells in the older adult, which has direct etiological linkages with many diseases. T cell development in the thymus is dependent on t...

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Autores principales: Zhao, Jin, Zhang, Zhenzhen, Lai, Kuan Chen, Lai, Laijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934747/
https://www.ncbi.nlm.nih.gov/pubmed/36798162
http://dx.doi.org/10.21203/rs.3.rs-2557067/v1
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author Zhao, Jin
Zhang, Zhenzhen
Lai, Kuan Chen
Lai, Laijun
author_facet Zhao, Jin
Zhang, Zhenzhen
Lai, Kuan Chen
Lai, Laijun
author_sort Zhao, Jin
collection PubMed
description BACKGROUND: Although the thymus continues to export T cells throughout life, it undergoes a profound involution/atrophy with age, resulting in decreased numbers of T cells in the older adult, which has direct etiological linkages with many diseases. T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produce a rFOXN1 fusion protein containing the N-terminal of CCR9, FOXN1 and a protein transduction domain. RESULTS: We show here that, when injected intravenously into aged mice, the rFOXN1 fusion protein migrates into the thymus and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ. CONCLUSIONS: Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in the older adult.
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spelling pubmed-99347472023-02-17 Recombinant FOXN1 fusion protein increases T cell generation in aged mice Zhao, Jin Zhang, Zhenzhen Lai, Kuan Chen Lai, Laijun Res Sq Article BACKGROUND: Although the thymus continues to export T cells throughout life, it undergoes a profound involution/atrophy with age, resulting in decreased numbers of T cells in the older adult, which has direct etiological linkages with many diseases. T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produce a rFOXN1 fusion protein containing the N-terminal of CCR9, FOXN1 and a protein transduction domain. RESULTS: We show here that, when injected intravenously into aged mice, the rFOXN1 fusion protein migrates into the thymus and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ. CONCLUSIONS: Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in the older adult. American Journal Experts 2023-02-08 /pmc/articles/PMC9934747/ /pubmed/36798162 http://dx.doi.org/10.21203/rs.3.rs-2557067/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Zhao, Jin
Zhang, Zhenzhen
Lai, Kuan Chen
Lai, Laijun
Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title_full Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title_fullStr Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title_full_unstemmed Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title_short Recombinant FOXN1 fusion protein increases T cell generation in aged mice
title_sort recombinant foxn1 fusion protein increases t cell generation in aged mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934747/
https://www.ncbi.nlm.nih.gov/pubmed/36798162
http://dx.doi.org/10.21203/rs.3.rs-2557067/v1
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