Matrisome Transcriptome Dynamics during Tissue Aging.

The extracellular matrix (ECM) is a complex three-dimensional network of macromolecules that provides structural support for the cells and plays a significant role in tissue homeostasis and repair. Growing evidence indicates that dysregulation of ECM remodeling contributes to various pathological conditions in the body, including age-associated diseases. In this work, gene expression data of normal human tissues obtained from the Genotype-Tissue Expression project, as well as data from MatrisomeDB 2.0, the ECM-protein knowledge database, are used to estimate the age-dependent matrisome transcriptome dynamics in the blood, heart, brain, liver, kidneys, lungs, and muscle. Differential gene expression (DE) analysis revealed dozens of matrisome genes encoding both structural elements of the ECM and ECM-associated proteins, which had a tissue-specific expression profile with age. Among common DE genes that changed expression with age in at least three tissues, COL18A1, MFAP1, IGFBP7, AEBP1, LTBP2, LTBP4, LG14, EFEMP1, PRELP, BGN, FAM20B, CTSC, CTSS, and CLEC2B were observed. The findings of the study also reveal that there are sex-specific alterations during aging in the matrisome gene expression. Taken together, the results obtained in this work may help in understanding the role of the ECM in tissue aging and might prove valuable for the future development of the field of ECM research in general.

Regulatory T Cells in Atherosclerosis: Is Adoptive Cell Therapy Possible?

Atherosclerosis is an insidious vascular disease with an asymptomatic debut and development over decades. The aetiology and pathogenesis of atherosclerosis are not completely clear. However, chronic inflammation and autoimmune reactions play a significant role in the natural course of atherosclerosis. The pathogenesis of atherosclerosis involves damage to the intima, immune cell recruitment and infiltration of cells such as monocytes/macrophages, neutrophils, and lymphocytes into the inner layer of vessel walls, and the accumulation of lipids, leading to vascular inflammation. The recruited immune cells mainly have a pro-atherogenic effect, whereas CD4+ regulatory T (Treg) cells are another heterogeneous group of cells with opposite functions that suppress the pathogenic immune responses. Present in low numbers in atherosclerotic plaques, Tregs serve a protective role, maintaining immune homeostasis and tolerance by suppressing pro-inflammatory immune cell subsets. Compelling experimental data suggest that various Treg cell-based approaches may be important in the treatment of atherosclerosis. Here we highlight the most recent advances in our understanding of the roles of FOXP3-expressing CD4+ Treg cells in the atherogenic process and discuss potential translational strategies for the treatment of atherosclerosis by Treg manipulation.

Homeostasis and the functional roles of CD4+ Treg cells in aging.

OBJECTIVE: An upward trend in life expectancy has been observed in a majority of developed countries and leading to increasing in aging-related diseases. Aging is a risk factor for the development of widespread clinical conditions such as cardiovascular and autoimmune diseases, cancer, infections. Although studies have been very active, the problem of aging still remains one of the most obscure aspects of human biology. Regulatory T (Treg) cells with immunosuppressive properties have a pivotal role in the maintenance of immune homeostasis. Alterations in Treg cell functionality appear to be of great importance in the development of immune senescence and contribute to increased susceptibility to immune-mediated diseases with age. DESIGN: This review highlights recent findings regarding the age-related changes in the numbers and functional activity of human Tregs. Some of the mechanisms that maintain the balance of Tregs during human aging are discussed. The possible roles of Tregs in the pathogenesis of diseases associated with advanced age are also considered. RESULTS: Age-related systemic changes, such as thymic involution, hormonal status, and epigenetic modifications, may affect the state of the Treg population and trigger various diseases. These changes involve decline or amplification in the functional activity of Tregs, an increase in the memory Treg subset and shifting of a Th17/Treg balance. CONCLUSION: Taken together, the reviewed data suggest equal or even increased Treg functionality with age. Thus, age-mediated Treg expansion and higher Treg activity may contribute to elevated immune suppression and increased risk of infections and cancer.

MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential.

Rheumatoid arthritis (RA) is a polygenic disease characterized by autoimmunity and systemic inflammation with progressive impairment of joints that results in lifelong disability and increased mortality. Early diagnosis and therapeutic intervention or treatment can prevent severe disease manifestations in patients suffering from RA. The use of appropriate predictive biomarkers may improve the efficiency of RA therapy. The general aim of this review is to highlight the most recent findings on miRNAs expression profiles in RA patients and to discuss their potential as new biomarkers for diagnostic purposes. The current literature demonstrates that a variety of miRNAs is frequently dysregulated in RA patients. To date, the majority of miRNAs have been found to be overexpressed during the natural course of RA. MiR-16, miR-146a/b, miR-150, miR-155, and miR-223 described here were shown to be overexpressed at the systemic level: in both the periphery and RA joints. Circulating peripheral blood miRNAs, especially miR-16, miR-21, miR-24, miR-26a, miR-125a-5p, miR-125b, miR-126-3p, miR-223, and miR-451, which are elevated in the plasma or serum, are considered to be the most promising non-invasive biomarkers for the detection of RA.