Functional regulation of monocyte-derived dendritic cells by microRNAs

Zhan, Yifan; Wu, Li

doi:10.1007/s13238-012-0042-0

Cited by 17 publications

(18 citation statements)

References 90 publications

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“…MiRNAs have emerged as important controllers of many cellular events, including TLR signaling (14). MicroRNAs have also been shown as an important link between the innate and adaptive immune systems, potentially playing a role in the pathogenesis of inflammatory diseases (15-19). The essential functions of miRNAs in many human disease processes have triggered robust interests and as a result, the first miRNA mimic, miR-122 mimic, has entered into the hepatitis C virus Phase 2 clinical trials (20).…”

Section: Introductionmentioning

confidence: 99%

miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection

Moon

Yang

Zheng

et al. 2014

The Journal of Immunology

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Bacterial infection and its associated sepsis are devastating clinical entities which lead to high mortality and morbidity in critically ill patients. Phagocytosis, along with other innate immune responses, exerts crucial impacts on the outcomes of these patients. MicroRNAs (miRNAs) are a novel class of regulatory noncoding RNAs targeting specific mRNAs for modulation of translation and expression of a targeted protein. The roles of miRNAs in host defense against bacterial sepsis remain unclear. We found that bacterial infections and/or bacterial-derived LPS enhanced the level of miR-15a/16 in bone marrow derived macrophages (BMDMs). Deletion of miR-15a/16 (miR-15a/16-/-) in myeloid cells significantly decreased the bacterial infection associated mortality in sepsis mouse models. Moreover, miR-15a/16 deficiency (miR-15a/16-/-) resulted in augmented phagocytosis and generation of mitochondrial reactive oxygen species (ROS) in BMDMs. Supportively, over-expression of miR-15a/16 using miRNA mimics led to decreased phagocytosis and decreased generation of mitochondrial ROS. Mechanistically, deletion of miR-15a/16 up-regulated the expression of toll-like receptor 4 (TLR4) via targeting the principle transcriptional regulator PU.1 locating on the promoter region of TLR4, and further modulated TLR4's downstream signaling molecules, including Rho GTPase Cdc 42 and TRAF6. Additionally, deficiency of miR-15a/16 also facilitated TLR4-mediated pro-inflammatory cytokine/chemokine release from BMDMs at the initial phase of infections. Taken together, miR-15a/16 altered phagocytosis and bacterial clearance by targeting, at least partially, on the TLR4-associated pathways, subsequently affecting the survival of septic mice.

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Section: Introductionmentioning

confidence: 99%

miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection

Moon

Yang

Zheng

et al. 2014

The Journal of Immunology

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“…2 Since 2010 it has been known that the causative mutations are mainly biallelic truncating mutations in a gene of unknown function, C16orf57, located at 16q21. 3,4 Three recent papers, including one in this issue of Blood, have reported that the gene encodes a protein that is essential for the processing and stability of U6 snRNA, a molecule with a crucial role in RNA splicing. 1,5,6 U6 snRNA along with 4 other snRNAs (U1, U2, U4 and U5) and their associated proteins make up the spliceosome complex that catalyses the removal of introns from mRNA.…”

Section: Org Frommentioning

confidence: 99%

“…While the fundamental differentiation program for DCs is laid down by specific transcription factors, increasingly it is recognized that fine-tuning of this program is likely to depend on an added layer of control mediated through microRNA (miRNA) expression. 3,4 MicroRNAs are a class of small noncoding RNAs that repress translation of target genes through their complementary binding to the 3Ј untranslated regions of mRNAs by repressing translation initiation, induction of transcript decapping and deadenylation, and degradation of the mRNA. Canonical miRNAs are initially transcribed as long primary transcripts that are then processed into mature 20-24 nucleotide (nt)-long miRNAs.…”

mentioning

confidence: 99%

miR-142 keeps CD4+ DCs in balance

Belz

2013

Blood

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“…Во-первых, это связано с тем, что моноциты, являясь составной частью системы мононуклеарных фагоцитов, играют важную роль в регуляции иммунных реакций [10,29,30]. Во-вторых, доказано, что дендрит-ные клетки, предшественниками некоторых по-пуляций которых являются моноциты, иниции-руют развитие адаптативного иммунитета, в том числе стимулируют развитие противоопухолевых иммунных реакций [15,28,36]. И, в третьих, мо-ноциты принимают участие в реализации вос-палительных процессов, роль которых при опу-холевом росте активно изучается [13,16,19,21].…”

Section: Introductionunclassified