Age‐dependent changes in the nervous and endocrine control of the thymus

Hannestad, Jonas; Monjil, Diego F.; Díaz-Esnal, Belén; Cobo, J; Vega, J.A.

doi:10.1002/jemt.20014

Cited by 10 publications

(11 citation statements)

References 87 publications

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“…Beyond doubt, the age-dependent variations in activity of individual subpopulations of TEC are quite complex, controlled in response to growth factors, locally formed in various thymic compartments, modulated by a great variety of neural, endocrine factors of extrathymic origin (for review see Garcia-Suarez et al 2003;Hannestad et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…(1) a decreased pool of hematopoietic precursors of thymocytes and inhibited process of thymocyte differentiation (Aspinall 2003;Min et al 2004), (2) alterations in the neuroendocrine control of the thymus, as well as in levels of locally acting growth factors, including cytokines and thymic hormones (Garcia-Suarez et al 2003;Hannestad et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments

et al. 2007

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Structural alterations in thymuses of female rats during the first 2 years of life were evaluated by morphometric analysis and, then, correlated with organization of epithelial cells in various thymic compartments, examined for their cytokeratin immunoreactivity. With an advancing age, the thymuses demonstrated morphological modifications related to maturation and senescence, the dynamics of which varied between particular thymic compartments, and involved subpopulations of thymic epithelial cells. In the entire period of life the most dynamic changes were found in the cortex while the medulla was demonstrated to be a rather "stable" region. Morphometric studies revealed a negative correlation between the volume of thymic cortex and medulla and age of rats and a linear, positive relationship between the volume of connective tissue compartment and age. Changes in organization of epithelial network in the medulla preceded those observed in the cortex. Decreased proliferative activity of subset of medullary cells, which probably represented a self-renewable population, was accompanied by alterations in the immunocytochemically characterized (cytokeratines) differentiation process. At the same period of life, hypertrophy and hyperplasia of superficial epithelial cells seems to functionally replace medullary cells. This process begins around 3rd month of life and expands on all thymic compartments. The first changes in the cortex appeared around 8th month and were connected with reduced cytokeratin immunoreactivity. The involution observed in older animals was preceded by age-related alterations in epithelial network pattern which, in the course of stable morphometric parameters (between 5th and 12th month), showed character of a structural and functional adaptation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments

et al. 2007

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“…The maintenance of peripheral T-cell numbers appears to be regulated via a thymus-independent homeostatic process involving expansion of mature peripheral T cells which results in a much more limited T-cell receptor (TCR) repertoire with age. While the precise mechanism(s) facilitating thymic involution has yet to be determined, it appears that this thymic loss is an active process involving a variety of factors including the loss and apoptosis of the thymocytes and supportive cell populations within the microenvironment, alterations in the appropriate signals from supporting stromal and epithelial cells, diminished progenitor cell recruitment and expansion and a decrease in steroid signaling essential for thymocyte development 17-25. Other factors which are yet to be identified may also be involved.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression

Lustig¹,

Carter²,

Bertak³

et al. 2009

Int. J. Med. Sci.

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The decline in adaptive immunity, naïve T-cell output and a contraction in the peripheral T cell receptor (TCR) repertoire with age are largely attributable to thymic involution and the loss of critical cytokines and hormones within the thymic microenvironment. To assess the molecular changes associated with this loss of thymic function, we used cDNA microarray analyses to examine the transcriptomes of thymocytes from mice of various ages ranging from very young (1 month) to very old (24 months). Genes associated with various biological and molecular processes including oxidative phosphorylation, T- and B- cell receptor signaling and antigen presentation were observed to significantly change with thymocyte age. These include several immunoglobulin chains, chemokine and ribosomal proteins, annexin A2, vav 1 and several S100 signaling proteins. The increased expression of immunoglobulin genes in aged thymocytes could be attributed to the thymic B cells which were found to be actively producing IgG and IgM antibodies. Upon further examination, we found that purified thymic T cells derived from aged but not young thymi also exhibited IgM on their cell surface suggesting the possible presence of auto-antibodies on the surface thymocytes with advancing age. These studies provide valuable insight into the cellular and molecular mechanisms associated with thymic aging.

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“…We demonstrated that the thyroid hormone T 3 modulates the thymic microenvironment, enhancing thymic endocrine function (as exemplified by thymulin secretion), as well as ECM production and ECM receptor expression, with consequent augmentation of in vitro thymocyte adhesion [2,9,[25][26][27]. Accordingly, we also showed the presence of nuclear T 3 receptors in thymocytes and various preparations of thymic microenvironmental cell types [26,28].…”

Section: Introductionmentioning

confidence: 61%

Triiodothyronine Modulates Thymocyte Migration

Ribeiro-Carvalho

Lima-Quaresma

Mouço³

et al. 2007

Scand J Immunol

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Triiodothyronine (T3) exerts several effects on thymus physiology. In this sense, T3 is known to stimulate thymic microenvironmental cells to enhance the production of extracellular matrix (ECM) moieties, which are relevant in thymocyte migration. Here, we further investigated the in vivo influence of T3 on ECM production, as well as on ECM‐related T‐cell migration events. For this, BALB/c mice were subjected to two protocols of T3 treatment: long‐term (30 days) i.p. daily T3 injections or short‐term (16 h) after a single T3 intrathymic injection. These two treatments did promote an enhancement in the expression of fibronectin and laminin, in both cortex and medullary regions of the thymic lobules. As revealed by the long‐term treatment, the expression of ECM protein receptors, including VLA‐4, VLA‐5 and VLA‐6, was also increased in thymocyte subsets issued from T3‐treated mice. We further used thymic nurse cells (TNC) as an in vitro system to study the ECM‐related migration of immature thymocytes in the context of thymic epithelial cells. Even a single intrathymic injection of T3 resulted in an increase in the ex vivo exit of thymocytes from TNC lymphoepithelial complexes. Accordingly, when we evaluated thymocyte migration in transwell chambers pre‐coated with ECM proteins, we found an increase in the numbers of migrating cells, when thymocytes were derived from T3‐treated mice. Overall, our data show that in vivo intrathymic short‐term i.p. long‐term T3 treatments are able to modulate thymocyte migration, probably via ECM‐mediated interactions.

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Age‐dependent changes in the nervous and endocrine control of the thymus

Cited by 10 publications

References 87 publications

Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments

Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments

Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression

Triiodothyronine Modulates Thymocyte Migration

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