MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis

Srivastava, Ankit; Nikamo, Pernilla; Lohcharoenkal, Warangkana; Li, Dongqing; Meisgen, Florian; Landén, Ning Xu; Ståhle, Mona; Pivarcsi, Andor; Sonkoly, Enikö

doi:10.1016/j.jaci.2016.07.025

Cited by 114 publications

(133 citation statements)

References 35 publications

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“…Upregulation of miR-203 in psoriatic plaques leads to downregulation of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions (Sonkoly et al, 2007). Recently, Srivastava and colleagues (2016) unveiled the role of miR-146a in psoriasis patients and mouse model. They observed the genetic deletion of miR-146a leads to earlier onset and induced skin inflammation (Srivastava et al, 2016).…”

Section: Micrornas In Specific Tissues and Disease Processesmentioning

confidence: 99%

“…Recently, Srivastava and colleagues (2016) unveiled the role of miR-146a in psoriasis patients and mouse model. They observed the genetic deletion of miR-146a leads to earlier onset and induced skin inflammation (Srivastava et al, 2016). Further, miR-217 expression was found to be down-regulated in psoriasis keratinocytes of psoriatic patients (Zhu et al, 2016).…”

Section: Micrornas In Specific Tissues and Disease Processesmentioning

confidence: 99%

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Are microRNAs true sensors of ageing and cellular senescence?

Williams

Smith

Kumar

et al. 2017

Ageing Research Reviews

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All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases. Genetics and epigenetics are reported to play large roles in accelerating and/or delaying the onset of age-related diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent molecular biology discoveries have revealed that microRNAs (miRNAs) are potential sensors of aging and cellular senescence. Due to miRNAs capability to bind to the 3’ untranslated region (UTR) of mRNA of specific genes, miRNAs can prevent the translation of specific genes. The purpose of our article is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging and senescence. Our article discusses the current understanding of cellular senescence, its interplay with miRNAs regulation, and how they both contribute to disease processes.

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Section: Micrornas In Specific Tissues and Disease Processesmentioning

confidence: 99%

Section: Micrornas In Specific Tissues and Disease Processesmentioning

confidence: 99%

Are microRNAs true sensors of ageing and cellular senescence?

Williams

Smith

Kumar

et al. 2017

Ageing Research Reviews

View full text Add to dashboard Cite

show abstract

“…In human primary keratinocytes, miR-146a inhibits the expression of many pro-inflammatory factors, including CCL5 and IL-8 (Meisgen et al , 2014; Rebane et al , 2014). miR-146a has been shown to act as anti-inflammatory miRNA in mouse models of AD (Rebane et al , 2014), irritant contact dermatitis (Urgard et al , 2016) and psoriasis (Srivastava et al , 2016). The single nucleotide polymorphism (SNP) rs2910164 located in miR-146a precursor has been suggested to be associated with psoriasis in Han Chinese population (Zhang et al , 2014) and among Caucasians (Srivastava et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Hermann

Runnel

Aab

et al. 2017

Journal of Investigative Dermatology

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miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In the present study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in lesional skin of psoriasis patients. The expression of miR-146a was about 2-fold higher than that of miR-146b in healthy human skin and it was more strongly induced by stimulation of pro-inflammatory cytokines in keratinocytes and fibroblasts. miR-146a/b target genes regulating inflammatory responses or proliferation were altered in the skin of psoriasis patients, among which FERMT1 was verified as direct target of miR-146a. In silico analysis of genome-wide data from >4,000 psoriasis cases and >8,000 controls confirmed a moderate association between psoriasis and genetic variants in miR-146a gene. Transfection of miR-146a/b suppressed and inhibition enhanced keratinocyte proliferation and the expression of psoriasis-related target genes. Enhanced expression of miR-146a/b-influenced genes was detected in cultured keratinocytes from miR-146a−/− and skin fibroblasts from miR-146a−/− and miR-146b−/− mice stimulated with psoriasis-associated cytokines as compared to wild type mice. Our results indicate that besides miR-146a, miR-146b is expressed and might be capable of modulation of inflammatory responses and keratinocyte proliferation in psoriatic skin.

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“…Furthermore, it is known that activation of IL-17 signalling is central in the pathogenesis of psoriasis. A study using an imiquimodinduced mouse model of psoriasis showed that genetic deficiency in miR-146a could lead to an earlier onset and exacerbated skin lesions, with increased expression of IL-17-induced keratinocyte-derived inflammatory mediators [65,66]. In patients with RA, miR-146a has also been shown to be up-regulated in the IL-17-producing T cells [65,66].…”

Section: Aberrant Expression Of Mirnasmentioning

confidence: 99%

“…A study using an imiquimodinduced mouse model of psoriasis showed that genetic deficiency in miR-146a could lead to an earlier onset and exacerbated skin lesions, with increased expression of IL-17-induced keratinocyte-derived inflammatory mediators [65,66]. In patients with RA, miR-146a has also been shown to be up-regulated in the IL-17-producing T cells [65,66]. Therefore, miR-146a could play a negative ncRNAs in T cells of SLE and RA patients regulatory role in the inflammatory response by influencing the expression of IL-17 and TNF-a.…”

Section: Aberrant Expression Of Mirnasmentioning

confidence: 99%

Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the role of aberrant expression of non-coding RNAs in T cells

Lai

Koo

et al. 2017

Clinical and Experimental Immunology

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Summary Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are RNA molecules that do not translate into protein. Both miRNAs and lncRNAs are known to regulate gene expression and to play an essential role in T cell differentiation and function. Both systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease, and rheumatoid arthritis (RA), a representative disease of inflammatory arthritis, are characterized by a complex dysfunction in the innate and adaptive immunity. T cells play a central role in cell-mediated immune response and multiple defects in T cells from patients with SLE and RA have been observed. Abnormality in T cell signalling, cytokine and chemokine production, T cell activation and apoptosis, T cell differentiation and DNA methylation that are associated closely with the aberrant expression of a number of miRNAs and lncRNAs have been implicated in the immunopathogenesis of SLE and RA. This review aims to provide an overview of the current state of research on the abnormal expression of miRNAs and lncRNAs in T cells and their roles in the immunopathogenesis of SLE and RA. In addition, by comparing the differences in aberrant expression of miRNAs and lncRNAs in T cells between patients with SLE and RA, controversial areas are highlighted that warrant further investigation.

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MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis

Abstract: Our results define a crucial role for miR-146a in modulating IL-17-driven inflammation in the skin.

Cited by 114 publications

References 35 publications

Are microRNAs true sensors of ageing and cellular senescence?

Are microRNAs true sensors of ageing and cellular senescence?

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the role of aberrant expression of non-coding RNAs in T cells

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