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Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells

Thymic epithelial cells (TECs) are essential for T cell development in the thymus, yet the mechanisms governing their differentiation are not well understood. Lin28, known for its roles in embryonic development, stem cell pluripotency, and regulating cell proliferation and differentiation, is expres...

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Autores principales: Xiao, Shiyun, Zhang, Wen, Li, Jie, Manley, Nancy R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588642/
https://www.ncbi.nlm.nih.gov/pubmed/37868985
http://dx.doi.org/10.3389/fimmu.2023.1261081
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author Xiao, Shiyun
Zhang, Wen
Li, Jie
Manley, Nancy R.
author_facet Xiao, Shiyun
Zhang, Wen
Li, Jie
Manley, Nancy R.
author_sort Xiao, Shiyun
collection PubMed
description Thymic epithelial cells (TECs) are essential for T cell development in the thymus, yet the mechanisms governing their differentiation are not well understood. Lin28, known for its roles in embryonic development, stem cell pluripotency, and regulating cell proliferation and differentiation, is expressed in endodermal epithelial cells during embryogenesis and persists in adult epithelia, implying postnatal functions. However, the detailed expression and function of Lin28 in TECs remain unknown. In this study, we examined the expression patterns of Lin28 and its target Let-7g in fetal and postnatal TECs and discovered opposing expression patterns during postnatal thymic growth, which correlated with FOXN1 and MHCII expression. Specifically, Lin28b showed high expression in MHCII(hi) TECs, whereas Let-7g was expressed in MHCII(lo) TECs. Deletion of Lin28a and Lin28b specifically in TECs resulted in reduced MHCII expression and overall TEC numbers. Conversely, overexpression of Lin28a increased total TEC and thymocyte numbers by promoting the proliferation of MHCII(lo) TECs. Additionally, our data strongly suggest that Lin28 and Let-7g expression is reliant on FOXN1 to some extent. These findings suggest a critical role for Lin28 in regulating the development and differentiation of TECs by modulating MHCII expression and TEC proliferation throughout thymic ontogeny and involution. Our study provides insights into the mechanisms underlying TEC differentiation and highlights the significance of Lin28 in orchestrating these processes.
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spelling pubmed-105886422023-10-21 Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells Xiao, Shiyun Zhang, Wen Li, Jie Manley, Nancy R. Front Immunol Immunology Thymic epithelial cells (TECs) are essential for T cell development in the thymus, yet the mechanisms governing their differentiation are not well understood. Lin28, known for its roles in embryonic development, stem cell pluripotency, and regulating cell proliferation and differentiation, is expressed in endodermal epithelial cells during embryogenesis and persists in adult epithelia, implying postnatal functions. However, the detailed expression and function of Lin28 in TECs remain unknown. In this study, we examined the expression patterns of Lin28 and its target Let-7g in fetal and postnatal TECs and discovered opposing expression patterns during postnatal thymic growth, which correlated with FOXN1 and MHCII expression. Specifically, Lin28b showed high expression in MHCII(hi) TECs, whereas Let-7g was expressed in MHCII(lo) TECs. Deletion of Lin28a and Lin28b specifically in TECs resulted in reduced MHCII expression and overall TEC numbers. Conversely, overexpression of Lin28a increased total TEC and thymocyte numbers by promoting the proliferation of MHCII(lo) TECs. Additionally, our data strongly suggest that Lin28 and Let-7g expression is reliant on FOXN1 to some extent. These findings suggest a critical role for Lin28 in regulating the development and differentiation of TECs by modulating MHCII expression and TEC proliferation throughout thymic ontogeny and involution. Our study provides insights into the mechanisms underlying TEC differentiation and highlights the significance of Lin28 in orchestrating these processes. Frontiers Media S.A. 2023-10-06 /pmc/articles/PMC10588642/ /pubmed/37868985 http://dx.doi.org/10.3389/fimmu.2023.1261081 Text en Copyright © 2023 Xiao, Zhang, Li and Manley https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Xiao, Shiyun
Zhang, Wen
Li, Jie
Manley, Nancy R.
Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title_full Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title_fullStr Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title_full_unstemmed Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title_short Lin28 regulates thymic growth and involution and correlates with MHCII expression in thymic epithelial cells
title_sort lin28 regulates thymic growth and involution and correlates with mhcii expression in thymic epithelial cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588642/
https://www.ncbi.nlm.nih.gov/pubmed/37868985
http://dx.doi.org/10.3389/fimmu.2023.1261081
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