Laios, K. The thymus gland in ancient Greek medicine. Hormones 17, 285–286 (2018).
Miller, J. The function of the thymus and its impact on modern medicine. Science 369, eaba2429 (2020).
Article CAS PubMed Google Scholar
Nikolich-Žugich, J. The twilight of immunity: emerging concepts in aging of the immune system. Nat. Immunol. 19, 10–19 (2018).
Li, Y. R. & Zúñiga-Pflücker, J. C. Thymus aging and immune reconstitution, progresses and challenges. Semin. Immunol. 70, 101837 (2023).
Article CAS PubMed Google Scholar
van den Broek, T. et al. Neonatal thymectomy reveals differentiation and plasticity within human naive T cells. J. Clin. Invest. 126, 1126–1136 (2016). This work provides clinical evidence for endogenous thymic regeneration in children with partial thymectomy.
Article PubMed PubMed Central Google Scholar
Kinsella, S. & Dudakov, J. A. When the damage is done: injury and repair in thymus function. Front. Immunol. 11, 1745 (2020).
Article CAS PubMed PubMed Central Google Scholar
Xiao, S. et al. Sublethal total body irradiation causes long-term deficits in thymus function by reducing lymphoid progenitors. J. Immunol. 199, 2701–2712 (2017).
Article CAS PubMed Google Scholar
Jaffe, H. L. The influence of the suprarenal gland on the thymus : I. Regeneration of the thymus following double suprarenalectomy in the rat. J. Exp. Med. 40, 325–342 (1924).
Article CAS PubMed PubMed Central Google Scholar
Marmorston-Gottesman, J. & Jaffe, H. L. Compensatory hypertrophy of the thymus gland in the rat. J. Exp. Med. 42, 413–418 (1925).
Article CAS PubMed PubMed Central Google Scholar
Gruver, A. L. & Sempowski, G. D. Cytokines, leptin, and stress-induced thymic atrophy. J. Leukoc. Biol. 84, 915–923 (2008).
Article CAS PubMed PubMed Central Google Scholar
Taves, M. D. & Ashwell, J. D. Glucocorticoids in T cell development, differentiation and function. Nat. Rev. Immunol. 21, 233–243 (2020).
Fletcher, A. L. et al. Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment. J. Immunol. 183, 823–831 (2009).
Article CAS PubMed Google Scholar
Klopack, E. T., Crimmins, E. M., Cole, S. W., Seeman, T. E. & Carroll, J. E. Social stressors associated with age-related T lymphocyte percentages in older US adults: evidence from the US Health and Retirement Study. Proc. Natl Acad. Sci. USA 119, e2202780119 (2022).
Article CAS PubMed PubMed Central Google Scholar
Hong, J. Y. et al. Long-term programming of CD8 T cell immunity by perinatal exposure to glucocorticoids. Cell 180, 847–861.e815 (2020).
Article CAS PubMed PubMed Central Google Scholar
Pazirandeh, A., Jondal, M. & Okret, S. Conditional expression of a glucocorticoid receptor transgene in thymocytes reveals a role for thymic-derived glucocorticoids in thymopoiesis in vivo. Endocrinology 146, 2501–2507 (2005).
Article CAS PubMed Google Scholar
Willich, E. in The Thymus: Diagnostic Imaging, Functions, and Pathologic Anatomy (eds Walter, E. et al.) 57–61 (Springer, 1992).
Kuhl, H. et al. The effect of sex steroids and hormonal contraceptives upon thymus and spleen on intact female rats. Contraception 28, 587–601 (1983).
Article CAS PubMed Google Scholar
Windmill, K. F., Meade, B. J. & Lee, V. W. Effect of prepubertal gonadectomy and sex steroid treatment on the growth and lymphocyte populations of the rat thymus. Reprod. Fertil. Dev. 5, 73–81 (1993).
Article CAS PubMed Google Scholar
Abramson, J. & Anderson, G. Thymic epithelial cells. Annu. Rev. Immunol. 35, 85–118 (2017).
Article CAS PubMed Google Scholar
Velardi, E., Dudakov, J. A. & van den Brink, M. R. Sex steroid ablation: an immunoregenerative strategy for immunocompromised patients. Bone Marrow Transplant. 50, S77–S81 (2015).
Article CAS PubMed PubMed Central Google Scholar
Lai, K.-P. Targeting thymic epithelia AR enhances T-cell reconstitution and bone marrow transplant grafting efficacy. Mol. Endocrinol. 27, 25–37 (2013).
Article CAS PubMed Google Scholar
Kovacs, W. J. & Olsen, N. J. Androgen receptors in human thymocytes. J. Immunol. 139, 490–493 (1987).
Article CAS PubMed Google Scholar
Dulos, G. J. & Bagchus, W. M. Androgens indirectly accelerate thymocyte apoptosis. Int. Immunopharmacol. 1, 321–328 (2001).
Article CAS PubMed Google Scholar
Velardi, E. et al. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling. J. Exp. Med. 211, 2341–2349 (2014). This work provides evidence of the direct regulation of the intrathymic Notch ligand DLL4 by androgen receptor signaling, which provides a molecular mechansim by which sex steroid inhibition boosts thymic function.
Article CAS PubMed PubMed Central Google Scholar
Chen, Y. Thymus-derived glucocorticoids mediate androgen effects on thymocyte homeostasis. FASEB J. 24, 5043–5051 (2010).
CAS PubMed PubMed Central Google Scholar
Tibbetts, T. A., Demayo, F., Rich, S., Conneely, O. M. & O’Malley, B. W. Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility. Proc. Natl Acad. Sci. USA 96, 12021–12026 (1999).
Article CAS PubMed PubMed Central Google Scholar
Dumont-Lagacé, M. et al. Qualitative changes in cortical thymic epithelial cells drive postpartum thymic regeneration. Front. Immunol. 10, 3118 (2019).
Laan, M., Haljasorg, U., Kisand, K., Salumets, A. & Peterson, P. Pregnancy-induced thymic involution is associated with suppression of chemokines essential for T-lymphoid progenitor homing. Eur. J. Immunol. 46, 2008–2017 (2016).
Article CAS PubMed Google Scholar
Paolino, M. et al. RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature 589, 442–447 (2021). This work provides strong evidence linking pregnancy outcomes to molecular rewiring in the thymus, resulting in thymic involution and production of Tregcells.
Article CAS PubMed Google Scholar
Billard, M. J., Gruver, A. L. & Sempowski, G. D. Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses. PLoS ONE 6, e17940 (2011).
Article CAS PubMed PubMed Central Google Scholar
Ross, E. A. Thymic function is maintained during Salmonella-induced atrophy and recovery. J. Immunol. 189, 4266–4274 (2012).
Article CAS PubMed Google Scholar
Deobagkar-Lele, M., Chacko, S. K., Victor, E. S., Kadthur, J. C. & Nandi, D. Interferon-γ- and glucocorticoid-mediated pathways synergize to enhance death of CD4+ CD8+ thymocytes during Salmonella enterica serovar Typhimurium infection. Immunology 138, 307–321 (2013).
留言 (0)