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Glatiramer Acetate Enhances Myeloid-Derived Suppressor Cell Function via Recognition of Paired Ig-like Receptor B.


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-?B pathways while promoting IL-10/TGF-? 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-? 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 (LILRBs), 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.

SUBMITTER: van der Touw W 

PROVIDER: S-EPMC6379207 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Glatiramer Acetate Enhances Myeloid-Derived Suppressor Cell Function via Recognition of Paired Ig-like Receptor B.

van der Touw William W   Kang Kyeongah K   Luan Yi Y   Ma Ge G   Mai Sunny S   Qin Lihui L   Bian Guanglin G   Zhang Ruihua R   Mungamuri Sathish Kumar SK   Hu Hong-Ming HM   Zhang Cheng Cheng CC   Aaronson Stuart A SA   Feldmann Marc M   Yang Wen-Chin WC   Chen Shu-Hsia SH   Pan Ping-Ying PY  

Journal of immunology (Baltimore, Md. : 1950) 20180801 6


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 pathw  ...[more]

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