Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through LPS3/GPR174

Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):332-338. doi: 10.1016/j.bbrc.2017.10.028. Epub 2017 Oct 7.

Abstract

Lysophosphatidylserine (LysoPS) has been shown to have lipid mediator-like actions to induce mast cell degranulation and suppress T lymphocyte proliferation. Recently, three G protein-coupled receptors (GPCRs), LPS1/GPR34, LPS2/P2Y10, and LPS3/GPR174, were found to react specifically with LysoPS, raising the possibility that LysoPS exerts its roles through these receptors. In this study, we show that LPS3 is expressed in various T cell subtypes and is involved in suppression of Interleukin-2 (IL-2) production in CD4 T cells. We found that LysoPS suppressed the IL-2 production from activated T cells at the mRNA and protein levels. In addition, LysoPS did not have such an effect on the splenocytes and CD4 T cells isolated from LPS3-deficient mice. In LPS3-deficient splenocytes and CD4 T cells, anti-CD3/anti-CD28-triggered IL-2 production is somewhat increased. Interestingly, LysoPS with various fatty acids was up-regulated upon T cell activation. The present study raised the possibility that LysoPS exerts its immunosuppressive roles by down-regulating IL-2 production through a LysoPS-LPS3 axis in T cells.

Keywords: G protein-coupled receptor; Interleukin-2; Lysophosphatidylserine; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • CD28 Antigens / antagonists & inhibitors
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Separation
  • Gene Expression Regulation
  • Interleukin-2 / genetics*
  • Interleukin-2 / immunology
  • Lysophospholipids / immunology
  • Lysophospholipids / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Primary Cell Culture
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / immunology
  • Receptors, Lysophospholipid / genetics*
  • Receptors, Lysophospholipid / immunology
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2 / immunology
  • Signal Transduction
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology

Substances

  • Antibodies
  • CD28 Antigens
  • CD3 Complex
  • G-protein-coupled receptor 34
  • GPR174 protein, mouse
  • Interleukin-2
  • Lysophospholipids
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Receptors, Purinergic P2
  • lysophosphatidylserine