Functional Insulin-Like Growth Factor-1/Insulin-Like Growth Factor-1 Receptor-Mediated Circuit in Human and Murine Thymic Epithelial Cells

Coelho, Valéria de Mello; Villa‐Verde, Déa Maria Serra; Farias-de-Oliveira, Désio Aurélio; Brito, José M.; Dardenne, Mireille; Savino, Wilson

doi:10.1159/000048230

Cited by 46 publications

(36 citation statements)

References 45 publications

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“…Second, it was recognized several years ago that GH and IGF-1 could stimulate the growth of thymic epithelial cells (TEC) which are needed to support thymic function, e.g., [69], [70]. Expanded numbers of TEC produce increased amounts of extracellular matrix material such as laminin that are essential for thymocyte adherence [71]. Third, PRL can act indirectly to support the proliferation of thymocytes by directly stimulating the production of IL-2.…”

Section: Gh Effects On the Thymusmentioning

confidence: 99%

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Redelman¹,

Taub

et al. 2008

Cellular Immunology

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Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins.

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Section: Gh Effects On the Thymusmentioning

confidence: 99%

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Redelman¹,

Taub

et al. 2008

Cellular Immunology

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“…(2). Moreover, the presence of IGF-1R in human TEC has been characterized and IGF-1 stimulates expression of laminin, fibronectin, VLA-5 and VLA-6 by these cells, thus demonstrating the functionality of IGF-1R in human TEC [112]. Like in rodents, several studies have shown that GH/IGF-1 axis exerts its effects on numerous thymic functions such as the proliferation of thymocytes, TEC growth, and TEC production of chemokines like CXCL12 and CCL25.…”

Section: The Somatotrope Gh/igf-1 Axis and Thymus Function In Humansmentioning

confidence: 88%

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

Goffinet¹,

Mottet²,

Kermani³

et al. 2011

IEMAMC

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Abstract:The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic proliferation of T-cell precursors, selection and output of both self-tolerant and competent effector T cells, as well as of natural regulatory T cells (nTreg). In the crosstalk between the neuroendocrine and immune systems, peptide hormones have been more and more implicated in immunomodulation for the last thirty years. The somatotrope growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in particular has been repeatedly shown to play a major regulatory role upon thymus function and T-cell development. This review will focus on the important thymotropic properties of the somatotrope GH/IGF-1 axis, and will try to discriminate these properties in function of the endocrine or paracrine/autocrine pathways involved in their mediation. Most importantly, in light of an increasing number of recent studies, GH and IGF-1 now appear as novel therapeutic agents that could be used for enhancing thymopoiesis in different cases of immune deficiencies, including aging-related immune dysfunction.Keywords: Thymus, growth hormone (GH), insulin-like growth factors (IGFs), HIV, growth hormone deficiency (GHD), Chagas disease. GENERAL INTRODUCTIONThe thymus is now considered as a crucial organ for maintenance of immune system homeostasis and the central lymphoid organ where occurs the generation of self-tolerant and competent naive T cells, as well as self-antigen specific natural Treg cells [1,2]. However, for a long time, the thymus has been regarded as an endocrine gland. In addition, the thymus now appears as a privileged site where the endocrine and immune systems intimately interact.A permanent crosstalk exists between the neuroendocrine and immune systems [3][4][5][6]. In addition to the strong modulation of immunity by glucocorticoids and sexual steroids, other hormones have been more and more involved in immunomodulation. Indeed, the somatotrope GH/IGF-1 axis, as well as prolactin and thyroid hormones [7], were shown to play an important regulatory role in T-cell development [8][9][10].GH is mainly synthesised in the anterior pituitary gland but can also be produced by immune cells [11,12]. GH has several biological actions in the immune system including regulation of thymopoiesis and T-cell development [13]. Nevertheless, it is uneasy to distinguish whether the thymotropic effects of GH are direct or mediated by IGF-1, as most *Address correspondence to this author at the University of Liege Center of Immunoendocrinology (CIL), Institute of Pathology CHU-B23, B-4000 Liege-Sart Tilman, Belgium; Tel: +32 43 66 25 50; Fax: +32 43 66 98 59; E-mail: vgeenen@ulg.ac.be of GH effects are driven by induction of IGF-1 and as IGF-1 has also been described as an endogenous factor in the thymic microenvironment [12]. The evolution of the research field has brought new insights that justify an overview update as some ancie...

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“…Similarly, acromegalic patients (pituitary gland produces excess GH) exhibit an increase in relative numbers of circulating CD4 T cells as compared to age-matched healthy individuals (Colao et al 2002a, b). IGF-1 receptors are also expressed by primary lymphoid tissues and immune cells (Abboud et al 1991;de Mello Coelho et al 2002;Kooijman et al 1995a, b;Verland and Gammeltoft 1989). Mice lacking IGF-1 were shown to possess fewer thymocytes and peripheral naive T cells compared to wild-type mice, but after treatment with IGF-1, thymocyte numbers and function were restored (Chu et al 2008).…”

Section: Growth Hormonesmentioning

confidence: 99%

Improving immunity in the elderly: current and future lessons from nonhuman primate models

Meyer

Kerns

Haberthur

et al. 2011

AGE

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The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability to sense and evaluate microbial threats and organize their elimination, while limiting damage to host tissues. This delicate balance is achieved through coordinated action of the innate and adaptive arms of the immune system. Aging results in several structural and functional changes in the immune system, often described under the umbrella term "immune senescence". Age-related changes affect both the innate and adaptive arms of the immune system and are believed to result in increased susceptibility and severity of infectious diseases, which is further exacerbated by reduced vaccine efficacy in the elderly. Therefore, multiple strategies to improve immune function in the aged are being investigated. Traditionally, studies on immune senescence are conducted using inbred specific pathogen free (SPF) rodents. This animal model has provided invaluable insight into the mechanisms of aging. However, the limited genetic heterogeneity and the SPF status of this model restrict the successful transfer of immunological discoveries between murine models and the clinical setting. More recently, nonhuman primates (NHPs) have emerged as a leading translational model to investigate immune senescence and to test interventions aimed at delaying/reversing agerelated changes in immune function. In this article, we review and summarize advances in immunorestorative approaches investigated in the NHP model system and discuss where the NHP model can support the development of novel therapeutics.

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Functional Insulin-Like Growth Factor-1/Insulin-Like Growth Factor-1 Receptor-Mediated Circuit in Human and Murine Thymic Epithelial Cells

Cited by 46 publications

References 45 publications

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

Improving immunity in the elderly: current and future lessons from nonhuman primate models

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