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

摘要: Lipid mediators influence immunity in myriad ways. For example, circulating sphingosine-1-phosphate (S1P) is a key regulator of lymphocyte egress. Although the majority plasma S1P bound to apolipoprotein M (ApoM) high-density lipoprotein (HDL) particle, immunological functions ApoM-S1P complex are unknown. Here we show that dispensable for trafficking yet restrains lymphopoiesis by activating S1P1 receptor on bone marrow progenitors. Mice lacked ApoM (Apom(-/-)) had increased proliferation Lin(-) Sca-1(+) cKit(+) haematopoietic progenitor cells (LSKs) and common lymphoid progenitors (CLPs) marrow. Pharmacological activation or genetic overexpression suppressed LSK CLP cell vivo. was stably associated with CLPs, which showed active signalling Moreover, ApoM-bound S1P, but not albumin-bound inhibited vitro. Upon immune stimulation, Apom(-/-) mice developed more severe experimental autoimmune encephalomyelitis, characterized lymphocytes central nervous system breakdown blood-brain barrier. Thus, ApoM-S1P-S1P1 axis compartment and, subsequently, adaptive responses. Unique biological imparted specific chaperones could be exploited novel therapeutic opportunities.