miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.
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.
Department of Periodontology, University of Illinois at Chicago, Chicago, Illinois, USA.
Afsar Raza
AR
Naqvi
Department of Periodontology, University of Illinois at Chicago, Chicago, Illinois, USA.
Jezrom B
JB
Fordham
Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA.
Balaji
B
Ganesh
Department of Periodontology, University of Illinois at Chicago, Chicago, Illinois, USA.
Salvador
S
Nares
D000818:Animals; D017951:Antigen Presentation; D060890:B7-H1 Antigen / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology* / Q000502:physiology
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C555159:MIRN142 microRNA, human; C543845:MIRN24 microRNA, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs