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辐射诱导的 mafB 基因是胸腺再生所必需的。

Radiation inducible MafB gene is required for thymic regeneration.

机构信息

Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama City, Wakayama, 641-8509, Japan.

Experimental Therapeutics Laboratory, University of South Australia Cancer Research Institute, Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.

出版信息

Sci Rep. 2021 May 17;11(1):10439. doi: 10.1038/s41598-021-89836-7.

Abstract

The thymus facilitates mature T cell production by providing a suitable stromal microenvironment. This microenvironment is impaired by radiation and aging which lead to immune system disturbances known as thymic involution. Young adult thymus shows thymic recovery after such involution. Although various genes have been reported for thymocytes and thymic epithelial cells in such processes, the roles of stromal transcription factors in these remain incompletely understood. MafB (v-maf musculoaponeurotic fibrosarcoma oncogene homolog B) is a transcription factor expressed in thymic stroma and its expression was induced a day after radiation exposure. Hence, the roles of mesenchymal MafB in the process of thymic regeneration offers an intriguing research topic also for radiation biology. The current study investigated whether MafB plays roles in the adult thymus. MafB/green fluorescent protein knock-in mutant (MafB) mice showed impaired thymic regeneration after the sublethal irradiation, judged by reduced thymus size, total thymocyte number and medullary complexity. Furthermore, IL4 was induced after irradiation and such induction was reduced in mutant mice. The mutants also displayed signs of accelerated age-related thymic involution. Altogether, these results suggest possible functions of MafB in the processes of thymic recovery after irradiation, and maintenance during aging.

摘要

胸腺通过提供合适的基质微环境来促进成熟 T 细胞的产生。这种微环境会受到辐射和衰老的损害,导致免疫系统紊乱,即胸腺萎缩。年轻成年的胸腺在经历这种萎缩后会恢复。尽管在这些过程中已经报道了各种基因在胸腺细胞和胸腺上皮细胞中的作用,但基质转录因子在这些过程中的作用仍不完全清楚。MafB(v-maf 肌肉骨骼纤维肉瘤癌基因同源物 B)是一种在胸腺基质中表达的转录因子,其表达在辐射暴露后一天被诱导。因此,间质 MafB 在胸腺再生过程中的作用也为辐射生物学提供了一个有趣的研究课题。本研究探讨了 MafB 是否在成年胸腺中发挥作用。通过测量胸腺大小、总胸腺细胞数和皮质复杂性,发现 MafB/green 荧光蛋白敲入突变体(MafB)小鼠在亚致死辐射后胸腺再生受损。此外,在照射后诱导了 IL4,而在突变小鼠中这种诱导减少了。突变小鼠还表现出加速的与年龄相关的胸腺萎缩迹象。总之,这些结果表明 MafB 在照射后胸腺恢复和衰老过程中的维持过程中可能具有功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/608f/8129107/b1ef939dde18/41598_2021_89836_Fig1_HTML.jpg

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