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The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jul 01; Vol. 203 (1), pp. 148-157. Date of Electronic Publication: 2019 May 22. - Publication Year :
- 2019
-
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 <superscript>low</superscript> 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.<br /> (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Subjects :
- Cell Differentiation
Cells, Cultured
Coculture Techniques
Gene Expression Regulation
Humans
Immunomodulation
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Intercellular Adhesion Molecule-3 genetics
Intercellular Adhesion Molecule-3 metabolism
Interleukin-10 metabolism
Interleukin-4 metabolism
Lymphocyte Activation
RNA, Small Interfering genetics
Receptor Cross-Talk
Dendritic Cells physiology
Lectins, C-Type metabolism
MicroRNAs genetics
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 203
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 31118225
- Full Text :
- https://doi.org/10.4049/jimmunol.1801108