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Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells

The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antig...

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Autores principales: Horie, Kenta, Namiki, Kano, Kinoshita, Kyouhei, Miyauchi, Maki, Ishikawa, Tatsuya, Hayama, Mio, Maruyama, Yuya, Hagiwara, Naho, Miyao, Takahisa, Murata, Shigeo, Kobayashi, Tetsuya J., Akiyama, Nobuko, Akiyama, Taishin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652284/
https://www.ncbi.nlm.nih.gov/pubmed/38022666
http://dx.doi.org/10.3389/fimmu.2023.1186154
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author Horie, Kenta
Namiki, Kano
Kinoshita, Kyouhei
Miyauchi, Maki
Ishikawa, Tatsuya
Hayama, Mio
Maruyama, Yuya
Hagiwara, Naho
Miyao, Takahisa
Murata, Shigeo
Kobayashi, Tetsuya J.
Akiyama, Nobuko
Akiyama, Taishin
author_facet Horie, Kenta
Namiki, Kano
Kinoshita, Kyouhei
Miyauchi, Maki
Ishikawa, Tatsuya
Hayama, Mio
Maruyama, Yuya
Hagiwara, Naho
Miyao, Takahisa
Murata, Shigeo
Kobayashi, Tetsuya J.
Akiyama, Nobuko
Akiyama, Taishin
author_sort Horie, Kenta
collection PubMed
description The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.
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spelling pubmed-106522842023-01-01 Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells Horie, Kenta Namiki, Kano Kinoshita, Kyouhei Miyauchi, Maki Ishikawa, Tatsuya Hayama, Mio Maruyama, Yuya Hagiwara, Naho Miyao, Takahisa Murata, Shigeo Kobayashi, Tetsuya J. Akiyama, Nobuko Akiyama, Taishin Front Immunol Immunology The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection. Frontiers Media S.A. 2023-11-02 /pmc/articles/PMC10652284/ /pubmed/38022666 http://dx.doi.org/10.3389/fimmu.2023.1186154 Text en Copyright © 2023 Horie, Namiki, Kinoshita, Miyauchi, Ishikawa, Hayama, Maruyama, Hagiwara, Miyao, Murata, Kobayashi, Akiyama and Akiyama 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
Horie, Kenta
Namiki, Kano
Kinoshita, Kyouhei
Miyauchi, Maki
Ishikawa, Tatsuya
Hayama, Mio
Maruyama, Yuya
Hagiwara, Naho
Miyao, Takahisa
Murata, Shigeo
Kobayashi, Tetsuya J.
Akiyama, Nobuko
Akiyama, Taishin
Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title_full Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title_fullStr Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title_full_unstemmed Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title_short Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
title_sort acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652284/
https://www.ncbi.nlm.nih.gov/pubmed/38022666
http://dx.doi.org/10.3389/fimmu.2023.1186154
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