CD69 Is a TGF-β/1α,25-dihydroxyvitamin D3 Target Gene in Monocytes

Wöbke, Thea K.; Knethen, Andreas von; Steinhilber, Dieter; Sorg, B.

doi:10.1371/journal.pone.0064635

Cited by 13 publications

(9 citation statements)

References 50 publications

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“…CD69 (increased by TGF-β, Table 1), an early activation marker antigen of lymphocytes, eosinophils and neutrophils, is a target gene of TGF-β in monocytes (24). TGF-β rapidly upregulated CD69 transcription via TAK1-mediated, p38 MAPK activation (25). CD69 expression on eosinophils was also significantly increased in asthmatic patients after exposure to allergen (26) whereas knock-down or administration of anti-CD69 dramatically increased airway eosinophils recruitment and enhanced Th2/Th17 response in the BAL (27).…”

Section: Resultsmentioning

confidence: 99%

RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils

Esnault

Dozmorov

et al. 2015

Immunology Letters

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Despite major advances in our understanding of TGF-β signaling in multiple cell types, little is known about the direct target genes of this pathway in human eosinophils. These cells constitute the major inflammatory component present in the sputum and lung of active asthmatics and their numbers correlate well with disease severity. During the transition from acute to chronic asthma, TGF-β levels rise several fold in the lung which drives fibroblasts to produce extracellular matrix (ECM) and participate in airway and parenchymal remodeling. In this report, we use purified blood eosinophils from healthy donors and analyze baseline and TGF-β responsive genes by RNA Seq, and demonstrate that eosinophils (PBE) express 7,981 protein-coding genes of which 178 genes are up-regulated and 199 genes are down-regulated by TGF-β. While 18 target genes have been previously associated with asthma and eosinophilic disorders, the vast majority have been implicated in cell death and survival, differentiation, and cellular function. Ingenuity pathway analysis revealed that 126 canonical pathways are activated by TGF-β including iNOS, TREM1, p53, IL-8 and IL-10 signaling. As TGF-β is an important cytokine for eosinophil function and survival, and pulmonary inflammation and fibrosis, our results represent a significant step toward the identification of novel TGF-β responsive genes and provide a potential therapeutic opportunity by selectively targeting relevant genes and pathways.

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Section: Resultsmentioning

confidence: 99%

RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils

Esnault

Dozmorov

et al. 2015

Immunology Letters

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“…10%). Stimulation with leptin, LPS or phorbol 12-myristate 13-acetate (PMA), however, has been shown to enhance CD69 levels 32 . Crosslinking of CD69 potently activates monocytes, resulting in the production of inflammation mediators and cytotoxicity 33 .…”

Section: Discussionmentioning

confidence: 99%

Cells´ Flow and Immune Cell Priming under alternating g-forces in Parabolic Flight

Moser¹,

Sun

et al. 2019

Sci Rep

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Gravitational stress in general and microgravity (µg) in particular are regarded as major stress factors responsible for immune system dysfunction in space. To assess the effects of alternating µg and hypergravity (hyper-g) on immune cells, the attachment of peripheral blood mononuclear cells (PBMCs) to adhesion molecules under flow conditions and the antigen-induced immune activation in whole blood were investigated in parabolic flight (PF). In contrast to hyper-g (1.8 g) and control conditions (1 g), flow and rolling speed of PBMCs were moderately accelerated during µg-periods which were accompanied by a clear reduction in rolling rate. Whole blood analyses revealed a “primed” state of monocytes after PF with potentiated antigen-induced pro-inflammatory cytokine responses. At the same time, concentrations of anti-inflammatory cytokines were increased and monocytes displayed a surface molecule pattern that indicated immunosuppression. The results suggest an immunologic counterbalance to avoid disproportionate immune responses. Understanding the interrelation of immune system impairing and enhancing effects under different gravitational conditions may support the design of countermeasures to mitigate immune deficiencies in space.

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“…5D this model was applied to predict the impact of microRNAs on CD69 protein expression using the following estimates of mRNA and microRNA copy numbers per cell. CD69 mRNA was barely detectable in resting cells and increased to ∼25.000 per 10 6 copies of B2M in activated Jurkat T cells [ 62 ]. Based on the presence of ∼215 copies of B2M per cell [ 63 ], activated T cells contain ∼6 copies of Cd69 mRNA per cell.…”

Section: Supporting Informationmentioning

confidence: 99%

microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes

et al. 2015

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The development and homeostasis of multicellular organisms relies on gene regulation within individual constituent cells. Gene regulatory circuits that increase the robustness of gene expression frequently incorporate microRNAs as post-transcriptional regulators. Computational approaches, synthetic gene circuits and observations in model organisms predict that the co-regulation of microRNAs and their target mRNAs can reduce cell-to-cell variability in the expression of target genes. However, whether microRNAs directly regulate variability of endogenous gene expression remains to be tested in mammalian cells. Here we use quantitative flow cytometry to show that microRNAs impact on cell-to-cell variability of protein expression in developing mouse thymocytes. We find two distinct mechanisms that control variation in the activation-induced expression of the microRNA target CD69. First, the expression of miR-17 and miR-20a, two members of the miR-17-92 cluster, is co-regulated with the target mRNA Cd69 to form an activation-induced incoherent feed-forward loop. Another microRNA, miR-181a, acts at least in part upstream of the target mRNA Cd69 to modulate cellular responses to activation. The ability of microRNAs to render gene expression more uniform across mammalian cell populations may be important for normal development and for disease.

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CD69 Is a TGF-β/1α,25-dihydroxyvitamin D3 Target Gene in Monocytes

Cited by 13 publications

References 50 publications

RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils

RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils

Cells´ Flow and Immune Cell Priming under alternating g-forces in Parabolic Flight

microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes

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