Thymic stromal cells: Roles in atrophy and age-associated dysfunction of the thymus

Cepeda, Sergio; Griffith, Ann V.

doi:10.1016/j.exger.2017.12.022

Cited by 40 publications

(41 citation statements)

References 106 publications

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“…Of particular interest is the observation that the thymus is remarkably sensitive to inflammation (e.g., sepsis or experimental LPS-induced thymic involution) and oxidative stress which leads to thymic involution that seems to be irreversible [79][80][81][82][83][84]. Deleterious pro-apoptotic effects on both thymus stromal cells and intrathymic T cells are underlying this phenomenon.…”

Section: Oxidative Stress Inflammation and Premature Immunological Amentioning

confidence: 99%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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Progressive loss of renal function is associated with a series of changes of the adaptive immune system which collectively constitute premature immunological ageing. This phenomenon contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the T cell part of the adaptive immune system is highlighted. Naïve T cell lymphopenia, in combination with the expansion of highly differentiated memory T cells, are the hallmarks of immunological ageing. The decreased production of newly formed T cells by the thymus is critically involved. This affects both the CD4 and CD8 T cell compartment and may contribute to the expansion of memory T cells. The expanding populations of memory T cells have a pro-inflammatory phenotype, add to low-grade inflammation already present in ESRD patients and destabilize atherosclerotic plaques. The effect of loss of renal function on the thymus is not reversed after restoring renal function by kidney transplantation and constitutes a long-term mortality risk factor. Promising results from animal experiments have shown that rejuvenation of the thymus is a possibility, although not yet applicable in humans.

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Section: Oxidative Stress Inflammation and Premature Immunological Amentioning

confidence: 99%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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“…On the contrary, the thymus, which reaches its maximal size and T cell output during early postnatal life, exhibits early thymic involution, a phenomenon that becomes even more prominent with advancing age [12,13,[18][19][20][21]. Although the size of the human thymus seems to remain unchanged throughout life under normal conditions [22], in other vertebrates, it declines during aging [23]. Nevertheless, in almost all vertebrates having a thymus, thymic cellularity is progressively decreased and replaced by adipose tissue over time, resulting in perturbation of the normal tissue architecture [14,21,24,25] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Even though age-associated thymic regression represents one of the most recognizable features of the aging immune system, the underlying mechanisms are not well understood [33]. Several candidates have been proposed, suggesting that thymic regression involves the interplay of various and different mechanisms ( Figure 2); interestingly, there are lines of evidence that in this complex process, the thymic stroma and especially the TECS are the most sensitive compartment [12,23,27,34]. A number of studies reported that sex steroid hormones, and especially androgens, contribute to ageassociated thymic involution [12,23,27,35] (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…Several candidates have been proposed, suggesting that thymic regression involves the interplay of various and different mechanisms ( Figure 2); interestingly, there are lines of evidence that in this complex process, the thymic stroma and especially the TECS are the most sensitive compartment [12,23,27,34]. A number of studies reported that sex steroid hormones, and especially androgens, contribute to ageassociated thymic involution [12,23,27,35] (Figure 2). This notion was based on the observations (a) that thymic involution, although beginning in early postnatal life, is more pronounced with the onset of puberty when sex steroid levels increase and (b) that high doses of sex steroid administration cause degeneration of the thymus (reviewed in [23]).…”

Section: Introductionmentioning

confidence: 99%

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Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Barbouti

Vasileiou

Evangelou

et al. 2020

Oxidative Medicine and Cellular Longevity

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The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed “thymic involution.” A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

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“…The thymus, as a central immune organ, is the main site for generation of naive T lymphocytes [43]. Thymus atrophy is considered to be a biomarker of immune system aging and is influenced by many factors, such as age, hormones, and gender [44].…”

Section: Discussionmentioning

confidence: 99%

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

Zhang

et al. 2020

Genes

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Thymic degeneration and regeneration are regulated by estrogen and androgen. Recent studies have found that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in organ development. In this study, RNA sequencing (RNA-seq) results showed that ovariectomy significantly affected 333 lncRNAs, 51 miRNAs, and 144 mRNAs levels (p < 0.05 and |log2fold change| > 1), and orchiectomy significantly affected 165 lncRNAs, 165 miRNAs, and 208 mRNA levels in the thymus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) were closely related to cell development and immunity. Next, we constructed two lncRNA–miRNA–mRNA networks using Cytoscape based on the targeting relationship between differentially expressed miRNAs (DEMs) and DEGs and differentially expressed lncRNAs (DELs) analyzed by TargetScan and miRanda. Besides, we screened DEGs that were significantly enriched in GO and in ceRNA networks to verify their expression in thymocytes and thymic epithelial cells (TECs). In addition, we analyzed the promoter sequences of DEGs, and identified 25 causal transcription factors. Finally, we constructed transcription factor-miRNA-joint target gene networks. In conclusion, this study reveals the effects of estrogen and androgen on the expression of miRNAs, lncRNAs, and mRNAs in mice thymus, providing new insights into the regulation of thymic development by gonadal hormones and non-coding RNAs.

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Thymic stromal cells: Roles in atrophy and age-associated dysfunction of the thymus

Cited by 40 publications

References 106 publications

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

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