Background/Purpose:   The Mer tyrosine kinase (Mertk) is necessary for optimal removal of apoptotic cells in animal models.  Its ligation by apoptotic cell-bound protein S and GAS 6 also leads to an associated suppression of innate immunity.  Thus, Mertk may have a role in controlling immune responses to antigens exposed on apoptotic cells.   Immunoreactivity to such antigens is a defining characteristic of systemic lupus erythematosus.  We therefore compared the level of expression of Mertk in leukocytes from the blood of normal human subjects and patients with lupus erythematosus (SLE).

Methods:   Tumor cell lines known to express Mertk at the mRNA level or by western blot were used to identify antibodies that could reliably detect the Mertk and the related Tyro3 kinase by immunofluorescence.  Flow cytometry of isolated peripheral blood mononuclear cells was subsequently used to compare the levels of Mertk and Tyro3 on leukocytes from the blood of SLE patients (n=23) and normal control individuals (n=14).   Monocytes were identified by their high expression of CD14 together with their forward and side scatter characteristics and in some experiments by their lack of CD15 expression. Myeloid dendritic cells were identified by their lack of lineage specific markers CD3, CD14, CD19, CD56, high expression of CD11c and low expression of CD123. Plasmacytoid dendritic cells were identified by their lack of lineage specific markers, their high expression of CD123, and low expression of CD11c, 

Results:   Mertk was detected on dendritic cells (DC) and monocytes from both normal individuals and from SLE patients. There was reduced Mertk expression on myeloid dendritic cells from SLE patients compared to controls (p<.03), whereas on plasmacytoid dendritic cells there was very low expression in both groups. For monocytes, high levels of Mertk expression were observed on the small CD16+ population, whereas the much larger CD16- population of monocytes expressed low levels of Mertk. There was no difference in monocyte Mertk expression on cells from SLE patients compared to controls.  Tyro3 was barely detectable on any peripheral blood leukocytes, and there were no statistical differences on its expression in any of the cell types examined.

Conclusion: Myeloid DC from lupus patients express lower levels of Mertk than cells from normal individuals.  Mertk expression on monocytes and plasmacytoid DC from SLE patients is not different from expression on cells from normal controls. Because Mertk is an important receptor for clearance of apoptotic cells and because DC Mertk expression regulates cytokine production, the observed lower expression of MertK on myeloid DC may lead to a lack of control of their activation and contribute to the hyper activation of immunity in lupus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-the-mer-receptor-tyrosine-kinase-on-peripheral-blood-mononuclear-cells-from-systemic-lupus-erythematosus-patients/