Folate receptor-β constitutes a marker for human proinflammatory monocytes

Jiayin Shen, Andrew R. Hilgenbrink, Wei Xia, Yang Feng, Dimiter S. Dimitrov, Michael B. Lockwood, Robert J. Amato, Philip S. Low

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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 (CD14highCD16) expresses the FR and that only CD14highCD16 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.

Original languageEnglish (US)
Pages (from-to)563-570
Number of pages8
JournalJournal of Leukocyte Biology
Volume96
Issue number4
DOIs
StatePublished - Oct 1 2014

Keywords

  • Folate targeting
  • Immunotherapy
  • Inflammation
  • Inflammatory subset

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