IGF-1 increases survival of CD4+ lineage in a 2D model of thymocyte/thymic stromal cell co-culture

Vieira, Larissa Fernanda de Araújo; Lins, Marvin Paulo; Porto, Felipe Lima; Smaniotto, Salete; Reis, Marlon M.

doi:10.1007/s11626-022-00730-6

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“…Moreover, it has been suggested that old animals with high circulating levels of IGF-I tend to have higher absolute peripheral blood CD4 + T-cell counts ( 147 ). In keeping with this finding, it has been shown that IGF-1 can induce in vitro proliferation of CD4 + thymocytes in a co-culture with thymic microenvironmental cells ( 148 ). The authors also observed that IGF-1 enhanced mRNA expression of the ThPOK encoding gene Zbtb7b , a transcriptional factor involved in the thymocyte commitment to the CD4 + T-cell lineage.…”

Section: Thymus Involution Can Be Reverted By the Activation/restorat...mentioning

confidence: 53%

Intrathymic somatotropic circuitry: consequences upon thymus involution

et al. 2023

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Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution.

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Section: Thymus Involution Can Be Reverted By the Activation/restorat...mentioning

confidence: 53%