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MiR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

ABSTRACT: Antigen uptake, processing and presentation by antigen presenting cells (APCs) are tightly coupled processes which consequently lead to the activation of innate and adaptive immune responses. However, the regulatory role of microRNA (miRNAs) in these critical pathways is poorly understood. In this study, we show that overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic cells. MiRNA mimic transfected APCs exhibit defects in antigen presentation (Ova and CMV antigen) to CD4+ T-cells leading to reduced cell proliferation. Using transgenic OT-II mice we demonstrated that this impairment in T-cell proliferation is specific to antigen provided i.e., Ova. Further, human T-cells co-cultured with miRNA transfected dendritic cells secrete low levels of T helper (Th)-1 polarization associated cytokines. Analysis of molecules regulating APC and T-cell receptor interaction shows miRNA-mediated induced expression of Programmed Death-Ligand 1 (PD-L1) which inhibits T-cell proliferation. Blocking PD-L1 with antibodies rescues miRNA-mediated inhibition of T cell priming by DCs. These results uncover regulatory functions of miR-24, miR-30b and miR-142-3p in pairing innate and adaptive components of immunity.

SUBMITTER: Naqvi AR

PROVIDER: S-EPMC5017188 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

Naqvi Afsar Raza AR Fordham Jezrom B JB Ganesh Balaji B Nares Salvador S

Scientific reports 20160909

Antigen uptake, processing and presentation by antigen presenting cells (APCs) are tightly coupled processes which consequently lead to the activation of innate and adaptive immune responses. However, the regulatory role of microRNA (miRNAs) in these critical pathways is poorly understood. In this study, we show that overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic cells. MiRNA mimic tr ...[more]

PMID: 27611009

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MiR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

Publications

miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

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