Journal
CELL BIOCHEMISTRY AND BIOPHYSICS
Volume 79, Issue 3, Pages 497-508Publisher
HUMANA PRESS INC
DOI: 10.1007/s12013-021-00988-9
Keywords
Lysophospholipid; Lysophosphatidylserine; GPCR; Phospholipase; Immune regulation
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LysoPS is an emerging lysophospholipid mediator that acts through G protein-coupled receptors and is mainly produced by the deacylation of phosphatidylserine. It stimulates degranulation of mast cells and has immune-modulatory functions through its specific GPCRs expressed in immune cells. Modulation of LysoPS signaling shows promise for therapies targeting immune diseases.
Lysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). LysoPS is detected in various tissues and cells and thought to be produced mainly by the deacylation of phosphatidylserine. LysoPS has been known to stimulate degranulation of mast cells. Recently, four LysoPS-specific G protein-coupled receptors (GPCRs) were identified. These GPCRs belong to the P2Y family which covers receptors for nucleotides and LPLs and are predominantly expressed in immune cells such as lymphocytes and macrophages. Studies on knockout mice of these GPCRs have revealed that LysoPS has immune-modulatory functions. Up-regulation of a LysoPS-producing enzyme, PS-specific phospholipase A(1), was frequently observed in situations where the immune system is activated including autoimmune diseases and organ transplantations. Therefore, modulation of LysoPS signaling appears to be a promising method for providing therapies for the treatment of immune diseases. In this review, we summarize the biology of LysoPS-producing enzymes and receptors, recent developments in LysoPS signal modulators, and prospects for future therapeutic applications.
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