Glatiramer acetate enhances myeloid-derived suppressor cell function via recognition of paired Ig-like receptor B

William Van Der Touw, Kyeongah Kang, Yi Luan, Ge Ma, Sunny Mai, Lihui Qin, Guanglin Bian, Ruihua Zhang, Sathish Kumar Mungamuri, Hong Ming Hu, Chengcheng Zhang, Stuart A. Aaronson, Marc Feldmann, Wen Chin Yang, Shu Hsia Chen, Ping Ying Pan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Glatiramer acetate (GA; Copaxone) is a copolymer therapeutic that is approved by the Food and Drug Administration for the relapsing-remitting form of multiple sclerosis. Despite an unclear mechanism of action, studies have shown that GA promotes protective Th2 immunity and stimulates release of cytokines that suppress autoimmunity. In this study, we demonstrate that GA interacts with murine paired Ig-like receptor B (PIR-B) on myeloid-derived suppressor cells and suppresses the STAT1/NF-κB pathways while promoting IL-10/TGF-β cytokine release. In inflammatory bowel disease models, GA enhanced myeloid-derived suppressor cell-dependent CD4 + regulatory T cell generation while reducing proinflammatory cytokine secretion. Human monocyte-derived macrophages responded to GA by reducing TNF-α production and promoting CD163 expression typical of alternative maturation despite the presence of GM-CSF. Furthermore, GA competitively interacts with leukocyte Ig-like receptors B (LILRB s ), the human orthologs of PIR-B. Because GA limited proinflammatory activation of myeloid cells, therapeutics that target LILRBs represent novel treatment modalities for autoimmune indications.

Original languageEnglish (US)
Pages (from-to)1727-1734
Number of pages8
JournalJournal of Immunology
Volume201
Issue number6
DOIs
StatePublished - Sep 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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