TY - JOUR
T1 - Glatiramer acetate enhances myeloid-derived suppressor cell function via recognition of paired Ig-like receptor B
AU - Van Der Touw, William
AU - Kang, Kyeongah
AU - Luan, Yi
AU - Ma, Ge
AU - Mai, Sunny
AU - Qin, Lihui
AU - Bian, Guanglin
AU - Zhang, Ruihua
AU - Mungamuri, Sathish Kumar
AU - Hu, Hong Ming
AU - Zhang, Cheng Cheng
AU - Aaronson, Stuart A.
AU - Feldmann, Marc
AU - Yang, Wen Chin
AU - Chen, Shu Hsia
AU - Pan, Ping Ying
PY - 2018/9/15
Y1 - 2018/9/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1701450
DO - 10.4049/jimmunol.1701450
M3 - Article
C2 - 30068593
AN - SCOPUS:85053129043
VL - 201
SP - 1727
EP - 1734
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -