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Open Access Research article

Increased expression of Mer tyrosine kinase in circulating dendritic cells and monocytes of lupus patients: correlations with plasma interferon activity and steroid therapy

Brendan A Hilliard12, Gaetano Zizzo12, Mehriban Ulas12, Margaret K Linan3, Jessica Schreiter4 and Philip L Cohen12*

Author Affiliations

1 Section of Rheumatology, Department of Medicine, Temple University School of Medicine, 3322 North Broad Street, Philadelphia, PA 19140, USA

2 Temple Autoimmunity Center, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA

3 Department of Public Health, Temple University, Philadelphia, PA 19122, USA

4 Janssen Research and Development, LLC, Spring House, PA 19002, USA

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Arthritis Research & Therapy 2014, 16:R76  doi:10.1186/ar4517

Published: 21 March 2014

Abstract

Introduction

The requirement for the immunoregulatory Mer tyrosine kinase (Mer) for optimal removal of apoptotic cells prompted us to look at its expression in systemic lupus erythematosus (SLE), in which apoptotic cell clearance is abnormal. We compared the levels of expression of Mer in normal human subjects and in patients with SLE.

Methods

We used flow cytometry of isolated peripheral blood mononuclear cells to compare the levels of Mer on leukocyte subsets. We used a Mer-specific enzyme-linked immunosorbent assay (ELISA) to quantify soluble Mer (sMer) in plasmas.

Results

Monocytes, CD1c+ myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from both normal individuals and from SLE patients expressed Mer. In both normal and SLE patients, the CD14++CD16+ subpopulation of monocytes expressed the highest levels of Mer, with somewhat lower levels on the CD14intCD16+ population. Mer levels on CD1c+ mDCs and pDCs, and sMer levels in blood were increased in SLE patients compared with controls. In patients, Mer levels on CD14intCD16+, CD14++CD16- monocytes, and CD1c+ dendritic cells correlated positively with type I interferon (IFN-I) activity detected in blood. In SLE patients treated with corticosteroids, Mer expression on monocytes correlated with prednisone dose, CD1c+ myeloid dendritic cells in patients treated with prednisone had higher levels of Mer expression than those in patients not receiving prednisone.

Conclusions

We found no global defect in Mer expression in lupus blood. In contrast, we observed increased levels of Mer expression in DC populations, which could represent a response to increased IFN-I in SLE patients. Enhanced Mer expression induced by corticosteroids may contribute to its beneficial effects in SLE.