Journal article

MicroRNA networks associated with active systemic juvenile idiopathic arthritis regulate CD163 expression and anti-inflammatory functions in macrophages through two distinct mechanisms

Do Thuy, Rachel Tan, Mark Bennett, Mario Medvedovic, Alexei A Grom, Nan Shen, Sherry Thornton, Grant S Schulert

JOURNAL OF LEUKOCYTE BIOLOGY | WILEY | Published : 2018

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy with features of autoinflammation. Monocytes and macrophages in SJIA have a complex phenotype with both pro- and anti-inflammatory properties that combine features of several well characterized in vitro conditions used to activate macrophages. An important anti-inflammatory phenotype is expression of CD163, a scavenger receptor that sequesters toxic pro-inflammatory complexes that is highly expressed in both active SJIA and macrophage activation syndrome (MAS). CD163 is most strongly up-regulated by IL-10 (M(IL-10)), and not by other conditions that reflect features seen in SJIA monocytes such as M(LPS+IC). Micro..

View full abstract

University of Melbourne Researchers

Grants

Awarded by Center of Excellence in Molecular Hematology


Awarded by Single Cell Phenotyping Core of the Cincinnati Rheumatic Diseases Resource Center from National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

We thank the Cell Processing and Manipulation Core in the Translational Cores, and Physicians and Nurses at CCHMC for obtaining and processing these samples. We also thank the CCHMC Translational Research Trials Office for providing the regulatory and administrative support for this endeavor. The Translational Cores are supported in part by the Children's Hospital Research Foundation as well as the Center of Excellence in Molecular Hematology (P30 DK090971). The RNA sequencing datasets described in this paper are available in the Gene Expression Omnibus repository (GSE104853).r This work was supported by the Single Cell Phenotyping Core of the Cincinnati Rheumatic Diseases Resource Center (P30-AR070549 and PO1-AR048929) from the National Institutes of Health to A.A.G., and a Scientist Deveopment Award from the Rheumatology Research Foundation and Procter Scholar Award from the Cincinnati Children's Research Foundation to G.S.S.