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Int Immunol. 2016 Jun;28(6):283-92. doi: 10.1093/intimm/dxv072. Epub 2015 Dec 29.

Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes.

Author information

1
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
2
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
3
Department of Anatomy, Kansai University of Health Sciences, Kumatori, Osaka 590-0482, Japan.
4
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
5
Department of Immunology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
6
Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan Genetic Engineering Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
7
Genetic Engineering Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
8
Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
9
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Life Science, Faculty of Science & Engineering, Kinki University, Higashi-Osaka-shi, Osaka 577-8502, Japan.
10
Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, Suita, Osaka 565-0871, Japan mmiyasak@orgctl.med.osaka-u.ac.jp.

Abstract

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

KEYWORDS:

endothelial cell; high endothelial venule; lymph node; lymphocyte transmigration; lysophosphatidic acid

PMID:
26714589
PMCID:
PMC4885216
DOI:
10.1093/intimm/dxv072
[Indexed for MEDLINE]
Free PMC Article

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