Role of mi<scp>R</scp>‐155 in the regulation of lymphocyte immune function and disease

Seddiki, Nabila; Brezar, Vedran; Ruffin, Nicolas; Lévy, Yves; Swaminathan, Sanjay

doi:10.1111/imm.12227

Cited by 151 publications

(128 citation statements)

References 62 publications

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“…miR-155 has also been reported to regulate T cell trafficking and function (51)(52)(53). T cells have been shown to accumulate in the brain and to contribute to endothelial injury and death associated with ECM (54).…”

Section: Resultsmentioning

confidence: 99%

miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria

Barker

Kim

et al. 2017

Mol Med

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miR-155 has been shown to participate in host response to infection and neuroinflammation via negative regulation of blood-brain barrier (BBB) integrity and T cell function. We hypothesized that miR-155 may contribute to the pathogenesis of cerebral malaria (CM). To test this hypothesis, we used a genetic approach to modulate miR-155 expression in an experimental model of cerebral malaria (ECM). In addition, an engineered endothelialized microvessel system and serum samples from Ugandan children with CM were used to examine anti-miR-155 as a potential adjunctive therapeutic for severe malaria. Despite higher parasitemia, survival was significantly improved in miR-155 -/-mice versus wild-type littermate mice in ECM. Improved survival was associated with preservation of BBB integrity and reduced endothelial activation, despite increased levels of proinflammatory cytokines. Pretreatment with antagomir-155 reduced vascular leak induced by human CM sera in an ex vivo endothelial microvessel model. These data provide evidence supporting a mechanistic role for miR-155 in host response to malaria via regulation of endothelial activation, microvascular leak and BBB dysfunction in CM.

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Section: Resultsmentioning

confidence: 99%

miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria

Barker

Kim

et al. 2017

Mol Med

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“…In addition, the potential therapeutic inhibition of miR-155 is hampered by the multifunctional role of this microRNA and could result in multiple unwanted side effects such as immunosuppression [39] and tumor growth [52].…”

Section: Limitations Of the Studymentioning

confidence: 99%

MicroRNA-155 aggravates ischemia–reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst

Eisenhardt

Weiss

Smolka³

et al. 2015

Basic Res Cardiol

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The inflammatory sequelae of ischemia-reperfusion injury (IRI) are a major causal factor of tissue injury in various clinical settings. MicroRNAs (miRs) are short, non-coding RNAs, which regulate protein expression. Here, we investigated the role of miR-155 in IR-related tissue injury. Quantifying microRNA-expression levels in a human muscle tissue after IRI, we found miR-155 expression to be significantly increased and to correlate with the increased expression of TNF-α, IL-1β, CD105, and Caspase3 as well as with leukocyte infiltration. The direct miR-155 target gene SOCS-1 was downregulated. In a mouse model of myocardial infarction, temporary LAD ligation and reperfusion injury resulted in a smaller area of necrosis in miR-155-/- animals compared to wildtype animals. To investigate the underlying mechanisms, we evaluated the effect of miR-155 on inflammatory cell recruitment by intravital microscopy and on the generation of reactive oxygen species (ROS) of macrophages. Our intravital imaging results demonstrated a decreased recruitment of inflammatory cells in miR-155-/- animals during IRI. The generation of ROS in leukocytic cells of miR-155-/- animals was also reduced. RNA silencing of the direct miR-155 target gene SOCS-1 abrogated this effect. In conclusion, miR-155 aggravates the inflammatory response, leukocyte infiltration and tissue damage in IRI via modulation of SOCS-1-dependent generation of ROS. MiR-155 is thus a potential target for the treatment or prevention of IRI.

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“…MiR-155 has been extensively described for its essential role in the normal immune function of B-cell and T-cell lymphocytes and dendritic cells, but also as a likely driver in some aggressive lymphomas such as Hodgkin's and diffuse large B-cell (Vigorito et al 2013;Seddiki et al 2014). It has been proposed that because miR-155 is oncogenic in lympho-proliferative disorders, this may be true for other cancers.…”

Section: Introductionmentioning

confidence: 99%

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

Goldgraben

Russell

Rueda

et al. 2015

RNA

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MicroRNAs are short (17-26) noncoding RNAs driving or modulating physiological and pathological cellular events. Overexpression of miR-155 is pathogenic in B-cell malignancy but was also reported in a number of solid tumors-in particular, in breast cancer, where its role remains unclear and often contradictory. Using representative cell line models, we sought to determine whether the discrepant miR-155 effects in breast cancer could be explained by the heterogeneity of the disease. The growth of six breast cancer cell lines transfected with several miRNA mimics was analyzed. We found MCF-7 cell growth to be inhibited by miR-155 and miR-145 mimics, both 23-nt long, but not by a number of shorter mimics, including a universal commercial negative control. Microarray and Western blot analyses revealed induction of apoptosis, associated with interferon-β after activation of the double-stranded RNA sensor pathway. 3 ′ Trimming of the miRNA mimics to 21 nt substantially reduced their growth-inhibitory potency. Mutating the canonical seed of the miR-155 mimic had no effect on the induced inhibition, which was abolished by mutating the miRNA seed of the artificial passenger strand. A panel of breast cancer cell lines showed a wide range of sensitivities to 23-mer mimics, broadly consistent with the sensitivity of the cell lines to Poly (I:C). We demonstrate two sources for nonspecific in vitro effects by miRNA mimics: duplex length and the artificial passenger strand. We highlight the danger of a universal 21-mer negative control and the importance of using matched seed mutants for reliable interpretation of phenotypes.

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Role of miR‐155 in the regulation of lymphocyte immune function and disease

Cited by 151 publications

References 62 publications

miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria

miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria

MicroRNA-155 aggravates ischemia–reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst

Double-stranded microRNA mimics can induce length- and passenger strand–dependent effects in a cell type–specific manner

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