MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

Riepsaame, Joey; Oudenaren, A. Van; Broeder, Berlinda J. H. den; IJcken, Wilfred F. J. van; Pothof, Joris; Leenen, Pieter J. M.

doi:10.3389/fimmu.2013.00353

Cited by 29 publications

(21 citation statements)

References 66 publications

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“…In contrast, pro-survival TRAF6-CD40 signalling might utilise Akt not altering the expressing of Ppef2. We observed down-regulation of Ppef2 expression also after spontaneous maturation of DCs in culture and other studies have shown similarities between LPS activated and spontaneously activated cells in vitro, when analysing microarray data (Riepsaame, van Oudenaren et al, 2013). The majority of changes in gene expression during DC-maturation are reductions of expression (Sanchez, McWilliams et al, 2007).…”

Section: Discussionsupporting

confidence: 74%

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells

Brocker¹,

Zwick²,

Ried

et al. 2018

Preprint

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Apoptotic cell death of Dendritic cells (DCs) is critical for immune homeostasis. Although intrinsic mechanisms controlling DC death have not been fully characterized up to now, experimentally enforced inhibition of DC-death causes various autoimmune diseases in model systems. We have generated mice deficient for Protein Phosphatase with EF-Hands 2 (Ppef2), which is selectively expressed in CD8 + DCs, but not in other related DC subtypes such as tissue CD103 + DCs. Ppef2 is down-regulated rapidly upon maturation of DCs by toll-like receptor stimuli, but not upon triggering of CD40. Ppef2-deficient CD8 + DCs accumulate the pro-apoptotic Bcl-2-like protein 11 (Bim) and show increased apoptosis and reduced competitve repopulation capacities. Furthermore, Ppef2 -/-CD8 + DCs have strongly diminished antigen presentation capacities in vivo, as CD8 + T cells primed by Ppef2 -/-CD8 + DCs undergo reduced expansion. In conclusion, our data suggests that Ppef2 is crucial to support survival of immature CD8 + DCs, while Ppef2 down-regulation during DC-maturation limits T cell responses.

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Section: Discussionsupporting

confidence: 74%

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells

Brocker¹,

Zwick²,

Ried

et al. 2018

Preprint

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“…These findings are consistent with our previous observation that miR-155 was the most upregulated miRNA in spinal cord microglia from SOD1 G93A mice. 8 Importantly, Csf1r is among the genes directly targeted by miR-155 35, 36 and it is known that microglia are absent in Csf1r −/− mice 37 or mice treated with CSF1R inhibitors. 38 In summary, we found profound loss of the unique molecular and functional signature in microglia associated with disease progression in SOD1 G93A mice.…”

Section: Resultsmentioning

confidence: 99%

Targeting miR‐155 restores abnormal microglia and attenuates disease in SOD1 mice

Butovsky

Jedrychowski

Cialic

et al. 2014

Annals of Neurology

309

285

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OBJECTIVE To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). METHODS Nanostring microRNA, microglia and immune gene profiles, protein mass spectrometry and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice. RESULTS In SOD1 mice we found loss of the molecular signature that characterizes microglia and increased expression of miR-155. There was loss of the microglial molecules P2ry12, Tmem119, Olfml3, transcription factors Egr1, Atf3, Jun, Fos, Mafb and the upstream regulators Csf1r, Tgfb1 and Tgfbr1 which are essential for microglial survival. Microglia biological functions were suppressed including phagocytosis. Genetic ablation of miR-155 increased survival in SOD1 mice by 51d in females and 27d in males and restored the abnormal microglia and monocyte molecular signatures. Disease severity in SOD1 males was associated with early upregulation of inflammatory genes including Apoe in microglia. Treatment of adult microglia with APOE suppressed the M0-unique microglia signature and induced a M1-like phenotype. miR-155 expression was increased in the spinal cord of both familial and sporadic ALS. Dysregulated proteins that we identified in human ALS spinal cord were restored in SOD1G93A/miR-155−/− mice. Intraventricular anti-miR-155 treatment derepressed microglial miR-155 targeted genes and peripheral anti-miR-155 treatment prolonged survival. INERPRETATION We found overexpression of miR-155 in the SOD1 mouse and in both sporadic and familial human ALS. Targeting miR-155 in SOD1 mice restores dysfunctional microglia and ameliorates disease. These findings identify miR-155 as a therapeutic target for the treatment of ALS.

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“…miRNA profiles changed significantly, between HSC and immature DC. GM‐CSF expanded, immature and lipopolysaccharide‐activated murine moDC also display distinct miRNA expression profiles . The requirement for miRNA for human moDC development from progenitors has also been shown with miR‐21 and miR‐34a both being implicated in this process …”

Section: Microrna and DC Differentiationmentioning

confidence: 91%

MicroRNAs affect dendritic cell function and phenotype

et al. 2015

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SummaryMicroRNA (miRNA) are small, non-coding RNA molecules that have been linked with immunity through regulating/modulating gene expression. A role for these molecules in T-cell and B-cell development and function has been well established. An increasing body of literature now highlights the importance of specific miRNA in dendritic cell (DC) development as well as their maturation process, antigen presentation capacity and cytokine release. Given the unique role of DC within the immune system, linking the innate and adaptive immune responses, understanding how specific miRNA affect DC function is of importance for understanding disease. In this review we summarize recent developments in miRNA and DC research, highlighting the requirement of miRNA in DC lineage commitment from bone marrow progenitors and for the development of subsets such as plasmacytoid DC and conventional DC. In addition, we discuss how infections and tumours modulate miRNA expression and consequently DC function.

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MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

Cited by 29 publications

References 66 publications

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells

Targeting miR‐155 restores abnormal microglia and attenuates disease in SOD1 mice

MicroRNAs affect dendritic cell function and phenotype

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MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

Cited by 29 publications

References 66 publications

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8+Dendritic Cells

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8+Dendritic Cells

Targeting miR‐155 restores abnormal microglia and attenuates disease in SOD1 mice

MicroRNAs affect dendritic cell function and phenotype

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Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8⁺Dendritic Cells