Dicer in immune cell development and function

Devasthanam, Anand S; Tomasi, Thomas B.

doi:10.3109/08820139.2013.863557

Cited by 21 publications

(14 citation statements)

References 61 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using a different model with a Lyz2-Cre strain, Dicer deletion resulted in an increase in giant cell formation of macrophages [16]. In both T and B- lymphocytes, Dicer deletion can result in aberrations in differentiation or activation, depending the cell type and stage of development in which Dicer function is inhibited [24]. In our study, loss of Dicer function in committed mast cell progenitors results in profound loss of tissue mast cell compartments, suggesting a critical role for miRNAs in mast cell differentiation, growth or migration.…”

Section: Resultsmentioning

confidence: 99%

Global microRNA expression is essential for murine mast cell development in vivo

Brandal

Kapur

et al. 2014

Experimental Hematology

View full text Add to dashboard Cite

microRNAs (miRNAs) are small, non-coding RNAs that have been shown to play a critical role in normal physiology and disease, such as hematopoietic development and cancer. However, their role in mast cell function and development is poorly understood. The major objective of this study was to determine how global miRNA expression affects mast cell physiology. The RNase III endonuclease, Dicer, is required for the processing of pre-miRNAs into mature miRNAs. To investigate the effect of global miRNA depletion on mast cells in vivo, we generated a mast cell-specific knock out of Dicer in mice. Transgenic mice (Mcpt5-Cre) that express Cre selectively in connective tissue mast cells were crossed with mice carrying the floxed conditional Dicer allele (Dicer fl/fl). Mcpt5-Cre x Dicer fl/fl mice with homozygous Dicer gene deletion in mast cells were found to have a profound mast cell deficiency with near complete loss of peritoneal, gastrointestinal, and skin mast cells. We examined the in vivo functional consequence of mast cell-specific Dicer deletion using an IgE-dependent passive systemic anaphylaxis (PSA) murine model. IgE sensitized wild type Mcpt5-Cre x Dicer +/+ and heterozygous Mcpt5-Cre x Dicer fl/+ mice show marked hypothermia with antigen; however, homozygous Mcpt5-Cre x Dicer fl/fl mice were completely unresponsive to antigen challenge. These studies suggest a critical role for Dicer and miRNA expression for establishment of tissue compartments of functional mast cells in vivo.

show abstract

Section: Resultsmentioning

confidence: 99%

Global microRNA expression is essential for murine mast cell development in vivo

Brandal

Kapur

et al. 2014

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…A floxed Dicer1 mice line, crossed with lines harboring Cre recombinase driven by tissue‐specific promoters, has been used to determine the tissue‐specific contribution of miRs, including those in immune cell lineages. While the exact nature of miRs in different immune cells may differ, nearly all cell types observed have reduced populations upon Dicer1 depletion, with those that survive displaying severely reduced function (reviewed in ). Conditional Dicer depletion in the lymphocytes, including B cells, CD4 + T cells, CD8 + T cells, T‐reg cells, and NK cells all resulted in decreased cell proliferation and loss of function.…”

Section: Total Microrna Regulation Of Immune Cell Functionsmentioning

confidence: 99%

MicroRNAs in neutrophils: potential next generation therapeutics for inflammatory ailments

Gurol

Zhou

Deng

2016

Immunological Reviews

View full text Add to dashboard Cite

Neutrophils play fundamental roles in both acute and chronic inflammatory conditions, and directly contribute to the immune pathologies in both infectious and autoimmune ailments. MicroRNAs (miRs) regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post-transcriptional regulation. Many miRs are expressed in restricted tissues, regulated by stress and disease, and are emerging as mediators for intercellular communication. MiR profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes. In addition, several miRs are in clinical development for various diseases. A short list of miRs that regulate hematopoiesis and neutrophil development is identified. Unfortunately, very limited information is available regarding how miRs regulate neutrophil migration and activation in vivo. Extensive future work is required, especially in animal models such as mice, to illustrate the pivotal and complex miR-mediated regulatory network. In addition, zebrafish, a vertebrate model organism with conserved innate immunity, potentiated by the availability of imaging and genetic tools, will provide a platform for rapid discovery and characterization of miRs that are relevant to neutrophilic inflammation. Advances in this field are expected to provide the foundation for highly selective miR-based therapy to manipulate neutrophils in infection and inflammatory disorders.

show abstract

“…An embryonic knockout of Dicer is lethal in mice [14]. Recent work has shown that Dicer plays a substantial role in the development and function of immune cells [15]. Mutations in Dicer are present in several types of cancer as well as other diseases [16].…”

Section: Introductionmentioning

confidence: 99%

The modulation of Dicer regulates tumor immunogenicity in melanoma

2016

Self Cite

View full text Add to dashboard Cite

MicroRNAs (miRs) are small non-coding RNAs that regulate most cellular protein networks by targeting mRNAs for translational inhibition or degradation. Dicer, a type III endoribonuclease, is a critical component in microRNA biogenesis and is required for mature microRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. For example, increased Dicer expression in melanoma is associated with more aggressive tumors (higher tumor mitotic index and depth of invasion) and poor patient prognosis. However, the role that Dicer plays in melanoma development and immune evasion remains unclear. Here, we report on a newly discovered relationship between Dicer expression and tumor immunogenicity. To investigate Dicer's role in regulating melanoma immunogenicity, Dicer knockdown studies were performed. We found that B16F0-Dicer deficient cells exhibited decreased tumor growth compared to control cells and were capable of inducing anti-tumor immunity. The decrease in tumor growth was abrogated in immunodeficient NSG mice and was shown to be dependent upon CD8+ T cells. Dicer knockdown also induced a more responsive immune gene profile in melanoma cells. Further studies demonstrated that CD8+ T cells preferentially killed Dicer knockdown tumor cells compared to control cells. Taken together, we present evidence which links Dicer expression to tumor immunogenicity in melanoma.

show abstract

Dicer in immune cell development and function

Cited by 21 publications

References 61 publications

Global microRNA expression is essential for murine mast cell development in vivo

Global microRNA expression is essential for murine mast cell development in vivo

MicroRNAs in neutrophils: potential next generation therapeutics for inflammatory ailments

The modulation of Dicer regulates tumor immunogenicity in melanoma

Contact Info

Product

Resources

About