The receptor tyrosine kinase MerTK regulates dendritic cell production of BAFF

The MerTK receptor tyrosine kinase is an important negative regulator of dendritic cell function and is required to prevent B cell autoimmunity in vivo. It is not currently known however, if any causal relationship exists between these two aspects of MerTK function. We sought to determine if dendrit...

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Published in:	Autoimmunity (Chur, Switzerland) Vol. 42; no. 3; pp. 183 - 197
Main Authors:	Gohlke, P. R., Williams, J. C., Vilen, B. J., Dillon, S. R., Tisch, R., Matsushima, G. K.
Format:	Journal Article
Language:	English
Published:	England Informa UK Ltd 01-01-2009 Taylor & Francis
Subjects:	Age Factors Animals Antibodies, Antinuclear - blood Antibodies, Antinuclear - immunology autoantibody Autoimmunity - physiology B cell survival B-Cell Activating Factor - blood B-Cell Activating Factor - metabolism B-Cell Activating Factor - pharmacology B-Lymphocytes - cytology B-Lymphocytes - physiology BAFF Bone Marrow Cells - cytology Bone Marrow Cells - drug effects c-Mer Tyrosine Kinase Cell Count Cell Differentiation - drug effects Cell Survival - physiology Chromatin - immunology Coculture Techniques dendritic cell Dendritic Cells - cytology Dendritic Cells - drug effects Dendritic Cells - metabolism Dendritic Cells, Follicular - cytology Dendritic Cells, Follicular - metabolism DNA - immunology Gene Expression - genetics Interferon-gamma - pharmacology Lipopolysaccharides - pharmacology MerTK Mice Mice, Inbred C57BL Mice, Knockout Proto-Oncogene Proteins - physiology Receptor Protein-Tyrosine Kinases - physiology Recombinant Proteins - pharmacology Spleen - cytology Spleen - metabolism Tumor Necrosis Factor Ligand Superfamily Member 13 - physiology
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Summary:	The MerTK receptor tyrosine kinase is an important negative regulator of dendritic cell function and is required to prevent B cell autoimmunity in vivo. It is not currently known however, if any causal relationship exists between these two aspects of MerTK function. We sought to determine if dendritic cells (DC) from mice lacking MerTK (mertk− / − mice) have characteristics that may aid in the development of B cell autoimmunity. Specifically, we found that mertk− / − mice contain an elevated number of splenic DC, and this population contains an elevated proportion of cells secreting the critical B cell pro-survival factor, B cell activating factor (BAFF). Elevated numbers of BAFF-secreting cells were also detected among mertk− / − bone marrow-derived dendritic cell (BMDC) populations. This was observed in both resting BMDC, and BMDC stimulated with lipopolysaccharide (LPS) or treated with exogenous apoptotic cells. We also found that DC in general have a pro-survival effect on resting B cells in co-culture. However, despite containing more BAFF-secreting cells, mertk− / − BMDC were not superior to C57BL/6 or baff-deficient BMDC at promoting B cell survival. Furthermore, using decoy receptors, we show that DC may promote B cell survival and autoimmunity through a BAFF-and a proliferation-inducing ligand-independent mechanism.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0891-6934 1607-842X
DOI:	10.1080/08916930802668586