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

Erina Hata, Naoko Sasaki, Akira Takeda, Kazuo Tohya, Eiji Umemoto, Noriyuki Akahoshi, Satoshi Ishii, Kana Bando, Takaya Abe, Kuniyuki Kano, Junken Aoki, Haruko Hayasaka, Masayuki Miyasaka

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalInternational immunology
Volume28
Issue number6
DOIs
Publication statusPublished - 2016 Jun 24

Keywords

  • Endothelial cell
  • High endothelial venule
  • Lymph node
  • Lymphocyte transmigration
  • Lysophosphatidic acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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