HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation (Nature 523:342, 2015)

報告日期: 2015/10/06
報告時間: 4:00/4:50
報告學生: 許文俐
講評老師: 徐麗君
附件下載: 下載[1496-1443052833-1.pdf] 

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

Date: 2015/10/ 06                                                                       Reporter: Hsu Wen-Li

The source: NATURE, 2015                                                           Advisor: Yan Shian-Jang

ABSTRACT

Circulating sphingosine-1-phosphate (S1P), a lipid mediator, influences immunity in myriad ways by regulating lymphocyte egress. Despite the majority binding of plasma S1P to apolipoprotein M (ApoM) in the high-density lipoprotein (HDL) particle, the immunological functions of ApoM–S1P complex have been independently established. This study displays that ApoM–S1P is not necessary for lymphocyte trafficking, but this complex is crucial for repressing lymphopoiesis through activing the S1P1 receptor on bone marrow lymphocyte progenitors. Based on the results from ApoM knockout mice, Lin- Sca-1+ cKit+ haematopoietic progenitor cells (LSKs) and common lymphoid progenitors (CLPs) have increased their proliferation in bone marrow; yet suppression of LSK and CLP cell proliferation in vivo with pharmacological activation or genetic overexpression of S1P1. It indicates ApoM was stably associated with bone marrow CLPs, which showed active S1P1 signaling in vivo. Furthermore, ApoM-bound S1P but not albumin-bound S1P suppressed lymphopoiesis in vitro; thus, upon immune stimulation, ApoM knockout mice induced serious experimental autoimmune encephalomyelitis, which is characterized by increased lymphocytes in the central nervous system and breakdown of the blood–brain barrier. Therefore, the ApoM–S1P–S1P1 signaling axis inhibits the lymphocyte compartment and, subsequently, adaptive immune responses. Unique biological functions imparted by specific S1P chaperones could be exploited for novel therapeutic opportunities.

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