Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling

Abstract

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress-mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

Protective Effect of Virgin Coconut Oil on Cyclophosphamide-induced Histological Changes in Lymphoid Tissues

“…23 The depletion of lymphocytes population in the thymus of rats receiving only CY is consistent with previous observations that revealed decreased cellularity in the thymus of rats given CY orally at a dose of 10mg/kg/day for 30 days; 19 these changes are most probably attributed to the cytotoxic effects of CY, predominantly on the lymphocytes and medullary epithelial cells, 24 and to its immunotoxic effects which induces apoptosis, hypocellularity, and atrophy in the thymus. 25 Reduction in lymphoid cellularity and alterations in the corticomedullary ratio, had been regarded as deleterious effect of xenobiotics on the thymus, and is considered as a highly sensitive indicator of immunotoxicant exposure. 26 The reduction in the lymphoid cellularity in spleen of CY treated rats is in agreement with previous studies that observed depletion of T lymphocytes in mice treated with a single dose of 4 mg, 27 and 200 mg/kg of CY, 28 and decreased cellularity in the spleen in rats treated daily with 10mg/kg CY for 30 days.…”

Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice

“…26,27) It has been reported that biological stresses, including diet-restriction, induce many types of inflammatory cytokines, which contribute to thymic involution. 9,28) However, the functional roles of inflammatory cytokines in thymic involution remain obscure.…”

“…8) With regards to the inflammatory process, the levels of glucocorticoids and inflammatory cytokines are elevated, which then contribute to thymic involution. 9) However, the signaling mechanisms involved in diet-restriction-induced thymic involution, or the induction of inflammatory cytokines associated with thymic involution, remain unclear.…”

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

“…IL-7 plays a central role in maintaining T cell homeostasis and serves as a key factor in the proliferation and survival of naive T cells ( 118 , 119 ). During thymic development, stromal and epithelial cells in the thymus produce IL-7 to promote CD8 + T cell differentiation in the thymus ( 120 ). Thymic production declines with age and, as a consequence, IL-7 levels may decrease during the aging process ( 121 ).…”