Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis

JCI Insight. 2018 Jun 7;3(11):e96492. doi: 10.1172/jci.insight.96492.


Lupus nephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Among the different types of lupus nephritis, intracapillary immune complex (IC) deposition and accumulation of monocytes are hallmarks of lupus nephritis class III and IV. The relevance of intracapillary ICs in terms of monocyte recruitment and activation, as well as the nature and function of these monocytes are not well understood. For the early focal form of lupus nephritis (class III) we demonstrate a selective accumulation of the proinflammatory population of 6-sulfo LacNAc+ (slan) monocytes (slanMo), which locally expressed TNF-α. Immobilized ICs induced a direct recruitment of slanMo from the microcirculation via interaction with Fc γ receptor IIIA (CD16). Interestingly, intravenous immunoglobulins blocked CD16 and prevented cell recruitment. Engagement of immobilized ICs by slanMo induced the production of neutrophil-attracting chemokine CXCL2 as well as TNF-α, which in a forward feedback loop stimulated endothelial cells to produce the slanMo-recruiting chemokine CX3CL1 (fractalkine). In conclusion, we observed that expression of CD16 equips slanMo with a unique capacity to orchestrate early IC-induced inflammatory responses in glomeruli and identified slanMo as a pathogenic proinflammatory cell type in lupus nephritis.

Keywords: Autoimmunity; Immunology; Monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / immunology*
  • Amino Sugars / metabolism
  • Animals
  • Antigen-Antibody Complex / administration & dosage
  • Antigen-Antibody Complex / immunology*
  • Antigen-Antibody Complex / metabolism
  • Biopsy
  • Capillaries / cytology
  • Capillaries / immunology
  • Capillaries / metabolism
  • Disease Models, Animal
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Jurkat Cells
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / immunology*
  • Kidney Glomerulus / pathology
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Male
  • Mice
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Primary Cell Culture
  • Receptors, IgG / antagonists & inhibitors
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • 6-sulfo-LacNac
  • Amino Sugars
  • Antigen-Antibody Complex
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunoglobulins, Intravenous
  • Receptors, IgG
  • TNF protein, human
  • Tumor Necrosis Factor-alpha