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Hormonal control of T-cell development in health and disease

Key Points

  • The thymus is the primary lymphoid organ responsible for the generation of T cells

  • Thymus physiology and T-cell development can be controlled by hormones, via a variety of endocrine and paracrine pathways

  • Microenvironmental cells in the thymus constitutively produce hormones that are typically secreted by the pituitary gland, such as growth hormone, prolactin, oxytocin and vasopressin

  • Glucocorticoids induce thymocyte depletion through caspase-dependent apoptosis, whereas growth hormone enhances thymocyte proliferation and migration

  • Considering the variety of the interactions between the endocrine, the nervous and the immune systems, dysfunctions in one of these systems can affect the other

  • Acute infection by Trypanosoma cruzi (the causative agent of Chagas disease) induces thymic atrophy through glucocorticoid-mediated thymocyte depletion, which can be counteracted by exogenous prolactin

Abstract

The physiology of the thymus, the primary lymphoid organ in which T cells are generated, is controlled by hormones. Data from animal models indicate that several peptide and nonpeptide hormones act pleiotropically within the thymus to modulate the proliferation, differentiation, migration and death by apoptosis of developing thymocytes. For example, growth hormone and prolactin can enhance thymocyte proliferation and migration, whereas glucocorticoids lead to the apoptosis of these developing cells. The thymus undergoes progressive age-dependent atrophy with a loss of cells being generated and exported, therefore, hormone-based therapies are being developed as an alternative strategy to rejuvenate the organ, as well as to augment thymocyte proliferation and the export of mature T cells to peripheral lymphoid organs. Some hormones (such as growth hormone and progonadoliberin-1) are also being used as therapeutic agents to treat immunodeficiency disorders associated with thymic atrophy, such as HIV infection. In this Review, we discuss the accumulating data that shows the thymus gland is under complex and multifaceted hormonal control that affects the process of T-cell development in health and disease.

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Figure 1: Intrathymic T-cell differentiation.
Figure 2: Immuno–neuro–endocrine interactions in the thymus.
Figure 3: GH signalling in TECs stimulates proliferation of T cells.
Figure 4: Trypanosoma cruzi infection and thymus homeostasis.

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Acknowledgements

Work in the authors' laboratories was supported with grants from CNPq, Capes, Faperj and Fiocruz (Brazil), FOCEM (Mercosur countries) and CNRS (France). The conjoint work was developed in the framework of the Fiocruz–CNRS International Associated Laboratory of Immunology and Immunopathology.

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All authors researched data for the article, wrote, reviewed and edited the manuscript before submission. D.A.M.-d.-C., A.L. and W.S. made substantial contribution to discussion of the content.

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Savino, W., Mendes-da-Cruz, D., Lepletier, A. et al. Hormonal control of T-cell development in health and disease. Nat Rev Endocrinol 12, 77–89 (2016). https://doi.org/10.1038/nrendo.2015.168

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