2015
DOI: 10.1159/000375160
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Perspectives for Improvement of the Thymic Microenvironment through Manipulation of Thymic Epithelial Cells: A Mini-Review

Abstract: Thymic involution during aging is a major reason for the decreased production of naive T cells and reduced immunity. Alterations within the thymic microenvironment, characterized by the loss of function of thymic epithelial cells (TECs) and fibro-adipogenetic transformation, seem to underlie this process, mainly through declining communication between thymic stromal cells and developing thymocytes. Specifically, the signaling mediated by cytokines and hormones secreted by TECs declines during aging. Many thera… Show more

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Cited by 25 publications
(24 citation statements)
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“…[31][32][33] The cortico-medullary tissue architecture is progressively lost, which occurs in parallel with a decline in the export of thymocytes. 34 This process affects the peripheral T-cell compartment, with a consequent decrease in immunoresponsiveness as an indivi dual ages. 35 In addition, the epithelial compartment of ageing mice is altered in both cortical and medullary regions, with reduced numbers of TECs (including mTECs expressing AIRE) and consequently reduced expression of PTAs, 36,37 which in theory favours the generation of autoimmune events in ageing individuals.…”
Section: T-cell Developmentmentioning
confidence: 99%
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“…[31][32][33] The cortico-medullary tissue architecture is progressively lost, which occurs in parallel with a decline in the export of thymocytes. 34 This process affects the peripheral T-cell compartment, with a consequent decrease in immunoresponsiveness as an indivi dual ages. 35 In addition, the epithelial compartment of ageing mice is altered in both cortical and medullary regions, with reduced numbers of TECs (including mTECs expressing AIRE) and consequently reduced expression of PTAs, 36,37 which in theory favours the generation of autoimmune events in ageing individuals.…”
Section: T-cell Developmentmentioning
confidence: 99%
“…Even so, a number of pre-clinical and clinical approaches to rejuvenate the organ have already been developed that result in substantial improvement in thymus function, such as sex steroid ablation and administration of GH and IL-7. 34,38 Thymic hormone-mediated circuits Hormonal control of the thymus includes both endocrine and paracrine/autocrine pathways that act on thymic microenvironment cells and thymocytes via specific hormone receptors. Accordingly, hormones regulate the proliferation and survival of both lymphoid and thymic microenvironment cells, as well as selection of the T-cell repertoire, which is a mechanism partly related to the modulation of TCR activation upon MHC-peptide binding.…”
Section: T-cell Developmentmentioning
confidence: 99%
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“…In this multicellular structure with different cell types and functions several minor stem cell populations can be found, in particular thymic epithelial progenitor cells/thymic epithelial stem cells (TEPC/TESC) [15, 16•], mesenchymal stem cells (MSC) [17,18] and lymphoid progenitor cells (LPC) [12,[19][20][21][22][23][24]. Of these, thymic epithelial cells (TEC) provide most of the specialist functions of the organ [25,26]. As the thymus is organized into two regions, the cortex and the medulla, also TEC are defined according to their localization as cortical (c) and medullar (m) TEC.…”
Section: Thymus Cell Architecture and Thymic Epithelial Cellsmentioning
confidence: 99%
“…Early thymus shares the same rudiment with parathyroid for development, [4] with original roles in enhancing reproductive system and adolescence growth, which gives obvious evidence as an erstwhile endocrine organ. [12,13] Yet, owing to inharmonic involution of thymic bioactivity and architecture, peripheral T-cell repertoire development could not match with EMT-CSC constant evolution, resulting in significant increase in clinical cancer incidence and keeping CSC/ EMT pool-targeted strategy an intractable dilemma. Thymic untimely involution may represent a disharmony for a still-evolving erst endocrine organ to the biological burden of lymphopoietic activity.…”
Section: Introductionmentioning
confidence: 99%