MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells

Karrich, Julien J.; Jachimowski, Loes C. M.; Libouban, Marion A.A.; Iyer, Anand M.; Brandwijk, Kim I. M.; Taanman-Kueter, Esther W. M.; Nagasawa, Maho; Jong, Esther C. de; Uíttenbogaart, Christel H.; Blom, Bianca

doi:10.1182/blood-2012-12-475087

Cited by 77 publications

(60 citation statements)

References 42 publications

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“…In our studies, we did not find CpG-or poly I:C-induced expression of miR-146a in THP-1 monocytes or macrophages, which suggests that there is specificity among endosomal TLRs in their differential regulation of miR-146a expression in human macrophages. Previous reports have demonstrated that CpG priming in the RAW264.7 cell line led to the disruption of IRAKs and development of crosstolerance to LPS or CpG [42] and that there was an increase in miR-146a expression in CpG-stimulated plasmacytoid dendritic cells [43]. Therefore, it is possible that CpG-induced miR-146a expression could be differentially regulated among the cells in the myeloid lineage and across species.…”

Section: Discussionmentioning

confidence: 96%

TLR4, TLR7/8 agonist-induced miR-146a promotes macrophage tolerance to MyD88-dependent TLR agonists

Nahid

Benso

Shin

et al. 2016

Journal of Leukocyte Biology

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TLRs facilitate the recognition of pathogens by immune cells and the initiation of the immune response, leading to the production of proinflammatory cytokines and chemokines. Production of proinflammatory mediators by innate immune cells, such as macrophages, is tightly regulated to facilitate pathogen clearance while limiting an adverse impact on host tissue. Exposure of innate immune cells to TLR ligands induces a state of temporary refractoriness to a subsequent exposure of a TLR ligand, a phenomenon referred to as “tolerance.” This study sought to evaluate the mechanistic regulation of TLR4 and TLR7/8 ligand-induced tolerance to other TLRs by microRNA-146a. With the use of THP-1 macrophages, as well as human classic and alternative macrophages, we demonstrate that priming with a TLR4 agonist (LPS) or a TLR7/8 agonist (R848) induces homologous and heterologous tolerance to various TLR ligands in macrophages, leading to the impaired production of cytokines and chemokines. We also demonstrate that overexpression of microRNA-146a is sufficient to mimic LPS or R848-induced hyporesponsiveness. Conversely, inhibition of microRNA-146a activity leads to LPS- or R848-induced TLR hyper-responsiveness in TLR signaling tolerance. Furthermore, we demonstrate that microRNA-146a dampens cytokine production following a primary stimulus with MyD88-dependent but not MyD88-independent TLR pathways. Collectively, these data provide comprehensive evidence of the central role of microRNA-146a in TLR signaling tolerance to plasma membrane, as well as endosomal TLR ligands in human macrophages.

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Section: Discussionmentioning

confidence: 96%

TLR4, TLR7/8 agonist-induced miR-146a promotes macrophage tolerance to MyD88-dependent TLR agonists

Nahid

Benso

Shin

et al. 2016

Journal of Leukocyte Biology

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“…recently, the involvement of pdcs was observed in the inhibition of apoptotic cell clearance in marginal zone macrophages 90 . The pdcs, after Tlr-7 and Tlr-9 stimulation, express mir-146a, which through negative feedback accomplishes the survival of pdcs while down-regulating Bcl2-a1 levels and causing apoptosis 91 . The next mir-146a target in pdcs, il-1 receptor-associated kinase (iraK)-1 of the myd88/ TraF6/iraK1 signalling pathway, inhibits the activation of NFкB (ref.…”

Section: Innate Immunity and Mirs And Slementioning

confidence: 99%

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

Hušáková¹

2016

BIOMED PAP

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Background. Small non-coding RNA molecules (miRs) are involved in immune cell maturation and function and might influence immunopathological processes of systemic lupus erythematosus (SLE) pathogenesis. Methods and Results. This paper presents the results of a literature search for publications dealing with the relationship between miRs and pathological factors related to SLE such as genetic background, immune dysregulation and gender-associated differences participating in SLE development. In SLE, distinct miRs are differentially expressed in SLE cells of innate and adaptive immunity. The miR-146a and miR-155 genes, among others, interfere with intracellular signalling pathways downstream of toll-like receptors 7 and 9 (TLR-7, TLR-9) and influences interferon (IFN)-type I synthesis in plasmacytoid dendritic cells. In T and B cells, miR-126, miR-21, miR-146a, miR-155, miR-1246 and others might influence gene expression by epigenetic modifications, support abnormal cytosine release, differentiation of cell subsets, B cell hyperactivity and autoantibody production. Besides, estrogen might up-and downregulate immunologically active miRs, which are potential mediators of hormonal influences in SLE development. Moreover, SLE genetic basis included some polymorphisms of the miR-146a gene, which varies across populations. Conclusion. Distinct miRs are differentially expressed in both SLE mice models and human patients and promote autoimmune features of immune processes. MiRs are important molecules modulating susceptibility to SLE as well as its onset, clinical diversity and progression.

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“…miR150 is required for the crosspresentation capacity of Langerhans cells (skinresident DCs) [45] . In addition, miR29b, miR 29c [46] , miR126 [47] , miR146a [40,48] , miR155, and miR221 [49] have been shown to regulate DC apoptosis and cytokine production.…”

Section: Mirnas and Dcsmentioning

confidence: 99%

“…Accumulating evidence highlights the importance of specific miRNAs in DC development, antigen presentation capacity, and cytokine release [39] . miR 146a [40] , miR155 [41] , and let7i [42] are involved in the maturation and functional state of DCs, while miR148/152 [43] and miR223 [44] are involved in their antigenpresentation capacity. miR150 is required for the crosspresentation capacity of Langerhans cells (skinresident DCs) [45] .…”

Section: Mirnas and Dcsmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD.

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MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells

Abstract: Key Points MiR-146a expression is induced by TLR ligation expressed in pDCs. MiR-146a regulates pDC effector functions, including cytokine production and costimulatory capacity.

Cited by 77 publications

References 42 publications

TLR4, TLR7/8 agonist-induced miR-146a promotes macrophage tolerance to MyD88-dependent TLR agonists

TLR4, TLR7/8 agonist-induced miR-146a promotes macrophage tolerance to MyD88-dependent TLR agonists

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

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