MiR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T-cell activation. (30th November 2021)

• Record Type: Journal Article
• Authors: Olsson, Anton M; Povoleri, Giovanni A M; Somma, Domenico; Ridley, Michael L; Rizou, Tatiana; Lalnunhlimi, Sylvine; Macdonald, Lucy; Rajasekhar, Megha; Martinez-Nunez, Rocio T; Kurowska-Stolarska, Mariola; Taams, Leonie S
• Is Part Of: Clinical and experimental immunology. Volume 207:Number 2(2022)
• Page Start: 188
• Page End: 198
• Publication Date: 2021-11-30
• Subjects: microRNA -- innate immunity -- monocyte -- immune regulation -- IL-10; Immunopathology -- Periodicals; 616.079
• DOI: 10.1093/cei/uxab016
• Languages: English
• ISSNs: 0009-9104

Abstract

Abstract: 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. Abstract : 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. Graphical Abstract: