Folate receptor-β constitutes a marker for human proinflammatory monocytes

J Leukoc Biol. 2014 Oct;96(4):563-70. doi: 10.1189/jlb.2AB0713-372R. Epub 2014 Jul 11.


Activated macrophages are commonly involved in the pathogenesis of inflammatory and autoimmune diseases and have been frequently reported to overexpress FR-β. Although FR-targeted therapies aimed at eliminating activated macrophages have shown promise for treating inflammatory diseases, little work has been performed to evaluate whether other hematopoietic cells might also express FR-β. Analysis of peripheral blood cells with a mAb to human FR-β reveals that only monocytes express FR-β. Molecular characterization of these circulating monocytes further demonstrates that solely the classic/proinflammatory subset (CD14(high)CD16(-)) expresses the FR and that only CD14(high)CD16(-) FR-β(+) monocytes also display the ability to bind folate-linked molecules. Confirmation that this subset of monocytes indeed constitutes the proinflammatory subpopulation was obtained by demonstrating coexpression of FR-β with other proinflammatory markers, including CCR2 and HLA-DR. Synovial monocytes from the joints of patients with RA were also shown to express FR-β. As inhibition of the chemotaxis of proinflammatory monocytes into sites of inflammation has been explored frequently as a means of controlling autoimmune diseases, demonstration that FR-β is uniquely expressed on this proinflammatory subpopulation offers a new strategy to suppress migration of inflammatory monocytes into sites of inflammation.

Keywords: folate targeting; immunotherapy; inflammation; inflammatory subset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Biomarkers / metabolism
  • Folate Receptor 2 / metabolism*
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Lipopolysaccharide Receptors / metabolism
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phenotype
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism


  • Biomarkers
  • Folate Receptor 2
  • Lipopolysaccharide Receptors