title: Increased soluble phagocytic receptors sMer, sTyro3 and sAxl and reduced phagocytosis in juvenile-onset systemic lupus erythematosus.
abstract: BACKGROUND
  The TAM-receptor tyrosine kinase family, Tyro3, Axl and Mer are key to apoptotic cell clearance. Reduced phagocytic clearance in systemic lupus erythematosus (SLE) leads to prolonged exposure of nuclear autoantigen to the immune system. Here we measure the levels of TAM receptors and the phagocytic capacity of monocytes and macrophages in juvenile-onset SLE (JSLE).
  
  
  METHODS
  Mer protein was measured on monocytes from JSLE, healthy control and JIA patients. JSLE, healthy control and JIA patients' plasma were analysed for soluble Mer (sMer), soluble Tyro3 (sTyro) and soluble Axl (sAxl). A phagocytosis assay measured the effect of JSLE serum on phagocytic potential of JSLE and control monocytes to engulf E. Coli bacteria and healthy macrophages to engulf apoptotic neutrophils.
  
  
  RESULTS
  Mer receptor expression was significantly decreased on JSLE monocytes compared to healthy controls. Plasma sMer, sTyro and sAxl were significantly increased in JSLE patients compared to controls (p < 0.05). Adult healthy control macrophages had significantly decreased phagocytosis of E. Coli and apoptotic neutrophils in the presence of 10% JSLE serum compared to control serum (p < 0.05).
  
  
  CONCLUSIONS
  JSLE patients have a decreased phagocytosis due to both serum and cell-derived factors. Significantly increased levels of sMer, sTyro3 and sAxl may be important factors contributing to the deficit in phagocytosis ability.
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: Lucy
authors: L
authors: Ballantine
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: Angela
authors: A
authors: Midgley
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: David
authors: D
authors: Harris
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: Ella
authors: E
authors: Richards
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: Sarah
authors: S
authors: Burgess
authors: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP UK.
authors: Michael W
authors: MW
authors: Beresford
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000293:Adolescent; D017668:Age of Onset; D017209:Apoptosis / Q000502:physiology; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; C028495:phagocytosis receptor; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human; D000076202:c-Mer Tyrosine Kinase; D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000094963:Axl Receptor Tyrosine Kinase
keywords: Juvenile-onset SLE; Phagocytosis; TAM receptor; apoptotic cell clearance