miR-155-overexpressing monocytes resemble HLA(high)ISG15(+) synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4(+) T-cell activation

miR-155 overexpression of healthy control blood monocytes confers a specific gene signature that bears similarities to that of RA synovial macrophages. miR-155-overexpressing monocytes induce polyfunctional CD4(+)T-cell activation. This study reaffirms and extends the association of miR-155 and joint inflammation in RA. MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14(+) cells and HLA(high)ISG15(+) synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.