Thymus Degeneration and Regeneration

被引:37
作者
Duah, Maxwell [1 ,2 ]
Li, Lingling [1 ,2 ]
Shen, Jingyi [1 ,2 ]
Lan, Qiu [1 ,2 ]
Pan, Bin [1 ,2 ]
Xu, Kailin [1 ,2 ]
机构
[1] Xuzhou Med Univ, Affiliated Hosp, Dept Hematol, Xuzhou, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Blood Dis Inst, Xuzhou, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
thymus; thymic epithelial cells; degeneration; regeneration; autoimmune; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; RECOMBINANT HUMAN INTERLEUKIN-7; DOUBLE-POSITIVE THYMOCYTES; EPIDERMAL-GROWTH-FACTOR; HEMATOPOIETIC STEM; T-CELLS; EPITHELIAL-CELLS; BONE-MARROW; IN-VIVO;
D O I
10.3389/fimmu.2021.706244
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immune system's ability to resist the invasion of foreign pathogens and the tolerance to self-antigens are primarily centered on the efficient functions of the various subsets of T lymphocytes. As the primary organ of thymopoiesis, the thymus performs a crucial role in generating a self-tolerant but diverse repertoire of T cell receptors and peripheral T cell pool, with the capacity to recognize a wide variety of antigens and for the surveillance of malignancies. However, cells in the thymus are fragile and sensitive to changes in the external environment and acute insults such as infections, chemo- and radiation-therapy, resulting in thymic injury and degeneration. Though the thymus has the capacity to self-regenerate, it is often insufficient to reconstitute an intact thymic function. Thymic dysfunction leads to an increased risk of opportunistic infections, tumor relapse, autoimmunity, and adverse clinical outcome. Thus, exploiting the mechanism of thymic regeneration would provide new therapeutic options for these settings. This review summarizes the thymus's development, factors causing thymic injury, and the strategies for improving thymus regeneration.
引用
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页数:17
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共 195 条
[1]   Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis [J].
Abrahamsson, Sofia V. ;
Angelini, Daniela F. ;
Dubinsky, Amy N. ;
Morel, Esther ;
Oh, Unsong ;
Jones, Joanne L. ;
Carassiti, Daniele ;
Reynolds, Richard ;
Salvetti, Marco ;
Calabresi, Peter A. ;
Coles, Alasdair J. ;
Battistini, Luca ;
Martin, Roland ;
Burt, Richard K. ;
Muraro, Paolo A. .
BRAIN, 2013, 136 :2888-2903
[2]   Thymic Epithelial Cells [J].
Abramson, Jakub ;
Anderson, Graham .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 35, 2017, 35 :85-118
[3]   Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention [J].
Aiello, Anna ;
Farzaneh, Farzin ;
Candore, Giuseppina ;
Caruso, Calogero ;
Davinelli, Sergio ;
Gambino, Caterina Maria ;
Ligotti, Mattia Emanuela ;
Zareian, Nahid ;
Accardi, Giulia .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[4]   Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation [J].
Akiyama, Nobuko ;
Shinzawa, Miho ;
Miyauchi, Maki ;
Yanai, Hiromi ;
Tateishi, Ryosuke ;
Shimo, Yusuke ;
Ohshima, Daisuke ;
Matsuo, Koichi ;
Sasaki, Izumi ;
Hoshino, Katsuaki ;
Wu, Guoying ;
Yagi, Shintaro ;
Inoue, Jun-ichiro ;
Kaisho, Tsuneyasu ;
Akiyama, Taishin .
JOURNAL OF EXPERIMENTAL MEDICINE, 2014, 211 (12) :2425-2438
[5]   The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance [J].
Akiyama, Taishin ;
Shimo, Yusuke ;
Yanai, Hiromi ;
Qin, Junwen ;
Ohshima, Daisuke ;
Maruyama, Yuya ;
Asaumi, Yukiko ;
Kitazawa, Juli ;
Takayanagi, Hiroshi ;
Penninger, Josef M. ;
Matsumoto, Mitsuru ;
Nitta, Takeshi ;
Takahama, Yousuke ;
Inoue, Jun-ichiro .
IMMUNITY, 2008, 29 (03) :423-437
[6]   Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells [J].
Akunuru, Shailaja ;
Geiger, Hartmut .
TRENDS IN MOLECULAR MEDICINE, 2016, 22 (08) :701-712
[7]   Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration [J].
Alpdogan, Ö ;
Hubbard, VM ;
Smith, OM ;
Patel, N ;
Lu, S ;
Goldberg, GL ;
Gray, DH ;
Feinman, J ;
Kochman, AA ;
Eng, JM ;
Suh, D ;
Muriglan, SJ ;
Boyd, RL ;
van den Brink, MRM .
BLOOD, 2006, 107 (06) :2453-2460
[8]   Central T cell tolerance: Identification of tissue-restricted autoantigens in the thymus HLA-DR peptidome [J].
Alvarez, Inaki ;
Collado, Javier A. ;
Colobran, Roger ;
Carrascal, Montserrat ;
Teresa Ciudad, M. ;
Canals, Francesc ;
James, Eddie A. ;
Kwok, William W. ;
Gaertner, Martina ;
Kyewski, Bruno ;
Pujol-Borrell, Ricardo ;
Jaraquemada, Dolores .
JOURNAL OF AUTOIMMUNITY, 2015, 60 :12-19
[9]   Thymic epithelial cells: the multi-tasking framework of the T cell "cradle" [J].
Alves, Nuno L. ;
Huntington, Nicholas D. ;
Rodewald, Hans-Reimer ;
Di Santo, James P. .
TRENDS IN IMMUNOLOGY, 2009, 30 (10) :468-474
[10]   Thymic epithelial cells: working class heroes for T cell development and repertoire selection [J].
Anderson, Graham ;
Takahama, Yousuke .
TRENDS IN IMMUNOLOGY, 2012, 33 (06) :256-263