miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation

Olsson, A. M. et al. (2022) miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation. Clinical and Experimental Immunology, 207(2), pp. 188-198. (doi: 10.1093/cei/uxab016) (PMID:35020867) (PMCID:PMC8982969)

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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 HLAhighISG15+ 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kurowska-Stolarska, Professor Mariola and MacDonald, Miss Lucy and Somma, Domenico
Authors: Olsson, A. M., Povoleri, G. A.M., Somma, D., Ridley, M. L., Rizou, T., Lalnunhlimi, S., MacDonald, L., Rajasekhar, M., Martinez-Nunez, R. T., Kurowska-Stolarska, M., and Taams, L. S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Clinical and Experimental Immunology
Publisher:Oxford University Press
ISSN:0009-9104
ISSN (Online):1365-2249
Published Online:30 November 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Clinical and Experimental Immunology 207(2): 188-198
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
304798Dissecting the role of distinct phenotypic clusters of synovial tissue macrophages in the regulation of joint homeostasis and the resolution of joint inflammation in Rheumatoid ArthritisMariola Kurowska-StolarskaVersus Arthritis (ARTRESUK)22272III - Immunology
303229RACE RenewalIain McInnesVersus Arthritis (ARTRESUK)NW/22072III - Immunology