miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection

Li, Qi Jing; Chau, Jacqueline; Ebert, Peter; Sylvester, Giselle; Min, Hye‐Young; Liu, Gwen; Braich, Ravi; Manoharan, Muthiah; Soutschek, Juergen; Skare, Petra; Klein, Lawrence O.; Davis, Mark M.; Chen, Chang Zheng

doi:10.1016/j.cell.2007.03.008

Cited by 1,052 publications

(1,049 citation statements)

References 44 publications

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“…For example, previous studies showed that miR‐181a regulates local immune balance (Liu et al ., 2012) and T‐cell sensitivity (Li et al ., 2007), although its mechanistic action remains unclear. We found that miR‐181a‐3p was coexpressed with and predicted to target three immune response genes, namely CXCL16 , RAB27A, and SPON2 .…”

Section: Discussionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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Section: Discussionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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“…In addition, miRNA have been found to control hematopoiesis (10), metabolism (11), and cardiac hypertrophy (12). It has been found that miRNA modulate T cell selection and T cell receptor sensitivity (13) as well as Treg cell development (14), which may suggest that miRNA are also involved in the development of autoimmunity. Recently, altered levels of miRNA have been linked to chronic inflammatory skin diseases (15).…”

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confidence: 99%

Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

Stańczyk

Pedrioli

Brentano

et al. 2008

Arthritis & Rheumatism

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Objective. MicroRNAs (miRNA) have recently emerged as a new class of modulators of gene expression. In this study we investigated the expression, regulation, and function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue.Methods. Locked nucleic acid microarray was used to screen for differentially expressed miRNA in RASFs treated with tumor necrosis factor ␣ (TNF␣). TaqMan-based real-time polymerase chain reaction was applied to measure the levels of miR-155 and miR-146a. Enforced overexpression of miR-155 was used to investigate the function of miR-155 in RASFs.Results

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“…4A,B). Previous studies conducted in mice demonstrated that SHP‐2 and DUSP5/6 were among several phosphatases controlled by miR‐181a, a ~22nt microRNA molecule capable of repressing the translation of over 40 phosphatases (Li et al ., 2007). Consistently, the progressive decline in miR‐181a levels observed in ageing human naïve CD4 + T cells dovetails the decreased T‐cell responsiveness following TCR stimulation (Li et al ., 2012).…”

Section: Resultsmentioning

confidence: 99%

“…The concept that miR‐181a acts as a rheostat for TCR signaling is not novel (Li et al ., 2007). Although expression of signaling molecules involved in TCR signaling is not influenced by age (Tamura et al ., 2000), cumulative homeostatic proliferation is believed to promote progressive loss of miR‐181a in ageing naïve T cells overtime (Li et al ., 2012).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐21 administration to aged mice rejuvenates their peripheral T‐cell pool by triggering de novo thymopoiesis

et al. 2016

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SummaryThe vaccination efficacy in the elderly is significantly reduced compared to younger populations due to thymic involution and age‐related intrinsic changes affecting their naïve T‐cell compartment. Interleukin (IL)‐21 was recently shown to display thymostimulatory properties. Therefore, we hypothesized that its administration to ageing hosts may improve T‐cell output and thus restore a competent peripheral T‐cell compartment. Indeed, an increase in the production of recent thymic emigrants (RTEs) attributable to intrathymic expansion of early thymic progenitors (ETPs), double‐negative (DN), and double‐positive (DP) thymocytes as well as thymic epithelial cell (TEC) was observed in recombinant (r)IL‐21‐treated aged mice. In sharp contrast, no alterations in the frequency of bone marrow (BM)‐derived progenitors were detected following rIL‐21 administration. Enhanced production of naïve T cells improved the T‐cell receptor (TCR) repertoire diversity and re‐established a pool of T cells exhibiting higher levels of miR‐181a and diminished amounts of the TCR‐inhibiting phosphatases SHP‐2 and DUSP5/6. As a result, stimulation of T cells derived from rIL‐21‐treated aged mice displayed enhanced activation of Lck, ZAP‐70, and ERK, which ultimately boosted their IL‐2 production, CD25 expression, and proliferation capabilities in comparison with T cells derived from control aged mice. Consequently, aged rIL‐21‐treated mice vaccinated using a tyrosinase‐related protein 2 (Trp2)‐derived peptide exhibited a substantial delay in B16 tumor growth and improved survival. The results of this study highlight the immunorestorative function of rIL‐21 paving its use as a strategy for the re‐establishment of effective immunity in the elderly.

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miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection

Cited by 1,052 publications

References 44 publications

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

Interleukin‐21 administration to aged mice rejuvenates their peripheral T‐cell pool by triggering de novo thymopoiesis

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