Lysophosphatidic acid receptors LPA4and LPA6differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes

High endothelial venules Extravasation Lymphocyte homing receptor Autotaxin Adoptive Cell Transfer
DOI: 10.1093/intimm/dxv072 Publication Date: 2015-12-30T01:44:36Z
ABSTRACT
Naive lymphocytes continuously migrate from the blood into lymph nodes (LNs) via high endothelial venules (HEVs). To extravasate HEVs, undergo multiple adhesion steps, including tethering, rolling, firm and transmigration. We previously showed that autotaxin (ATX), an enzyme generates lysophosphatidic acid (LPA), is highly expressed in ATX/LPA axis plays important role lymphocyte transmigration across HEVs. However, detailed mechanism underlying this axis's involvement has remained ill-defined. Here, we show two LPA receptors, LPA4 LPA6, are selectively on HEV cells (ECs) a major HEVs mice. In absence of expression, accumulated heavily within EC layer, compared to wild-type (WT) This accumulation was also observed LPA6 but it less pronounced. Adoptive transfer experiments using WT revealed deficiency ECs specifically compromised process, whereas effect not significant. These results indicate signals evoked differentially regulate extravasation peripheral LNs.
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