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

Autor:	Horie K; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan., Namiki K; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Kinoshita K; Graduate School of Engineering, The University of Tokyo, Tokyo, Japan., Miyauchi M; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan., Ishikawa T; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Hayama M; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Maruyama Y; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Hagiwara N; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan., Miyao T; YCI Laboratory for Immunological Transcriptomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan., Murata S; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan., Kobayashi TJ; Institute of Industrial Science, The University of Tokyo, Tokyo, Japan., Akiyama N; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Akiyama T; Laboratory for Immune Homeostasis, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.; Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Nov 02; Vol. 14, pp. 1186154. Date of Electronic Publication: 2023 Nov 02 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1186154
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Horie, Namiki, Kinoshita, Miyauchi, Ishikawa, Hayama, Maruyama, Hagiwara, Miyao, Murata, Kobayashi, Akiyama and Akiyama.)
Databáze:	MEDLINE
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