HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation

We show that apolipoprotein M -Sphingosine 1-phosphate is dispensable for lymphocyte trafficking yet restrains lymphopoiesis by activating the S1P1 receptor on bone marrow lymphocyte progenitors

Victoria A. Blaho; Sylvain Galvani; Eric Engelbrecht; Catherine Liu; Steven L. Swendeman; Mari Kono; Richard L. Proia; Lawrence Steinman; May H. Han; Timothy Hla

2015

Scholarcy highlights

  • Activation of S1P1 receptor on immune cells residing in secondary lymphoid organs and thymus is critical for lymphocyte egress into circulation
  • Unique biological functions imparted by specific Sphingosine 1-phosphate chaperones could be exploited for novel therapeutic opportunities
  • To determine the cause of lymphocytosis seen in Apom−/− mice, we examined hematopoietic cell populations in blood and bone marrow
  • To examine the role of S1P in progenitor proliferation regulated by apolipoprotein M+high-density lipoprotein, WT and Apom−/− mice were treated with SEW2871 and BM cell BrdU incorporation examined
  • ApoM+HDL-mediated suppression of lymphopoiesis was blocked by preincubation of HDL with an anti-S1P IgM28 but not by an irrelevant IgM. These findings suggest that ApoM+HDL-bound S1P is critical to restrain lymphocyte progenitor differentiation and proliferation
  • Our studies indicate that ApoM+HDL-mediated regulation of lymphocyte ontogeny impacts the extent and intensity of autoimmune neuroinflammation in the EAE model

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