Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and prolonged survival in two murine models of systemic lupus erythematosus

Bindu Varghese, Nicholas Haase, Philip S. Low

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease involving deposition of immune complexes in normal tissues and the consequent accumulation of immune cells and tissue injury. Activated macrophages are thought to contribute to disease pathogenesis by releasing inflammatory mediators that both cause direct tissue damage and attract other immune cells that augment inflammation. Previous studies in animal models of rheumatoid arthritis have shown that activated macrophages express a folate receptor that can be targeted with folate-linked haptens, leading to (1) marking of the activated macrophages with highly immunogenic haptens, (2) recognition of the marked cells by Fc receptor-expressing immune cells, and (3) destruction of the antibody-coated macrophages by the body's own immune system. Here we demonstrate that the same folate-hapten-targeted immunotherapy can greatly suppress symptoms of SLE in two animal models of the disease, resulting in reduced immune complex deposition, diminished damage to normal tissues, and prolonged animal survival.

Original languageEnglish (US)
Pages (from-to)679-685
Number of pages7
JournalMolecular pharmaceutics
Volume4
Issue number5
DOIs
StatePublished - Sep 2007

Keywords

  • Folate
  • Folate receptor
  • Immunotherapy
  • Lupus
  • Macrophage
  • SLE

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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