The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function

Abstract

MicroRNAs are small, noncoding RNAs that function as posttranscriptional modulators of gene expression by binding target mRNAs and inhibiting translation. They are therefore crucial regulators of several biological as well as immunological events. Recently, miR-511-3p has been implicated in the development and differentiation of APCs, such as dendritic cells (DCs), and regulating several human diseases. Interestingly, miR-511-3p is embedded within the human MRC1 gene that encodes the mannose receptor. In this study, we sought to examine the impact of miR-511-3p up-or downregulation on human DC surface phenotype, cytokine profile, immunogenicity (using IDO activity as a surrogate), and downstream T cell polarization. Using gene silencing and a selection of microRNA mimics, we could successfully suppress or induce the expression of miR-511-3p in DCs. Consequently, we show for the first time, to our knowledge, that inhibition and/or overexpression of miR-511-3p has opposing effects on the expression levels of two key C-type lectin receptors, namely the mannose receptor and DC-specific ICAM 3 nonintegrin at protein and mRNA levels, thereby affecting C-type lectin receptor-induced modulation of IDO activity in DCs. Furthermore, we show that downregulation of miR-511-3p drives an anti-inflammatory DC response characterized by IL-10 production. Interestingly, the miR-511-3p low DCs also promoted IL-4 secretion and suppressed IL-17 in cocultures with autologous T cells. Together, our data highlight the potential role of miR-511 in regulating DC function and downstream events leading to Th polarization and immune modulation.

MicroRNA-511-3p mediated modulation of the peroxisome proliferator-activated receptor gamma (PPARγ) controls LPS-induced inflammatory responses in human monocyte derived DCs

“…the level of PPARγ relative to miR-511-3p) indicated by an increase in PPARγ expression when miR-511-3p is low and vice versa, when miR-511-3p expression is high. It is important to note that transfection with either miR-511-3p inhibitors or mimics did not result in loss of cell viability as determined by Annexin-V staining (Figure S1) and did not impact monocyte to DC differentiation as we have previously demonstrated (24).…”

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

“…In this study, we have provided evidence that the increased AHR and lung inflammation due to the lack of Mrc1 can be reversed by AAV-mediated transduction of miR-511-3p. Furthermore, by gene array analysis, we have iden- the regulation of intestinal inflammation (20), and affects DC function by cross-talk with CLRs (21). Recent studies have also suggested that miR-511-3p may be a prognostic factor and potential tumor suppressor through inverse regulation of its downstream target gene AKT (serine/threonine-specific protein kinase 3) (34).…”

“…miR-511-3p is transcriptionally coregulated with the MRC1 gene in macrophages (10,19). Recent studies have suggested that miR-511-3p controls the activation of tumor-associated macrophages (19), regulates intestinal inflammation by targeting Toll-like receptor 4 (TLR4) (20), and affects dendritic cell (DC) function by cross-talk with CLRs (21). Profiling of macrophages demonstrated opposing expression patterns for miR-511 in M1 and M2 macrophages, with an increased expression of miR-511-3p in M2, but decreased expression in M1 macrophages (22).…”

Depletion of miR‐21 in dendritic cells aggravates renal ischemia‐reperfusion injury

“…miR‐511‐3p was also reported to be implicated in the development and differentiation of DCs. A recent study by Awuah et al 17 revealed that miR‐511‐3p could modulate immunogenicity of DCs through regulating the expression of mannose receptor and DC‐specific ICAM 3 nonintegrin. miR‐511‐3p knockdown induced an anti‐inflammatory DC response and promoted immune suppression.…”