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Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration.

ABSTRACT: Lymphocyte trafficking and migration through vascular endothelial cells (ECs) in secondary lymphoid tissues is critical for immune protection. In the present study, we investigate the role of nectin cell adhesion molecules for the migration of lymphocytes through ECs. Nectins are key players for the establishment of homotypic and heterotypic cell to cell contacts; they are required for cell to cell adherens junction formation and take part in the transendothelial migration of monocytes during the step of diapedesis, when monocytes migrate through EC junctions. We first show that Nectin-3 (CD113) is the only nectin expressed by T lymphocytes and since nectins are expressed on ECs we explored Nectin-3 potential functions in lymphocyte: EC interactions. We demonstrate that Nectin-2, expressed on ECs, is the major counter-receptor of Nectin-3. A soluble form of Nectin-3 binds to Nectin-2 localized at EC junctions and blocking Nectin-2 trans-interactions with monoclonal antibodies abolishes the binding of soluble Nectin-3 to ECs. Nectin-2 is expressed on High Endothelial venules (HEVs), where lymphocyte homing occurs in vivo. Finally, we show that Nectin-3 trans-interaction with Nectin-2 is essential for the process of lymphocyte transendothelial migration in vitro as targeting with blocking monoclonal antibodies either Nectin-3, expressed on lymphocytes, or Nectin-2, expressed on ECs, inhibits lymphocyte extravasation. The nectin family of CAMs is important for the regulation of endothelial barrier functions and transendothelial migration of immune cells. Our results demonstrate for the first time that Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and monocyte extravasation.

SUBMITTER: Devilard E

PROVIDER: S-EPMC3792040 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration.

Devilard Elisabeth E Xerri Luc L Dubreuil Patrice P Lopez Marc M Reymond Nicolas N

PloS one 20131007 10

Lymphocyte trafficking and migration through vascular endothelial cells (ECs) in secondary lymphoid tissues is critical for immune protection. In the present study, we investigate the role of nectin cell adhesion molecules for the migration of lymphocytes through ECs. Nectins are key players for the establishment of homotypic and heterotypic cell to cell contacts; they are required for cell to cell adherens junction formation and take part in the transendothelial migration of monocytes during th ...[more]

PMID: 24116228

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Project description:BACKGROUND:Mesenchymal stem cells (MSCs) are known to home to injured and inflamed regions via the bloodstream to assist in tissue regeneration in response to signals of cellular damage. However, the factors and mechanisms that affect their transendothelial migration are still unclear. In this study, the mechanisms involved in interleukin-1? (IL-1?) enhancing the transendothelial migration of MSCs were investigated. METHODS:Immunofluorescence staining and Western blotting were used to observe IL-1?-induced CXC chemokine receptor 3 (CXCR3) expression on MSCs. Quantitative real-time PCR and ELISA were used to demonstrate IL-1? upregulated both chemokine (C-X-C motif) ligand 9 (CXCL9) mRNA and CXCL9 ligand secretion in human umbilical vein endothelial cells (HUVECs). Monolayer co-cultivation, agarose drop chemotaxis, and transwell assay were conducted to investigate the chemotaxis invasion and transendothelial migration ability of IL-1?-induced MSCs in response to CXCL9. RESULTS:In this study, our immunofluorescence staining showed that IL-1? induces CXCR3 expression on MSCs. This result was confirmed by Western blotting. Following pretreatment with protein synthesis inhibitor cycloheximide, we found that IL-1? induced CXCR3 on the surface of MSCs via protein synthesis pathway. Quantitative real-time PCR and ELISA validated that IL-1? upregulated both CXCL9 mRNA and CXCL9 ligand secretion in HUVECs. In response to CXCL9, chemotaxis invasion and transendothelial migration ability were increased in IL-1?-stimulated MSCs. In addition, we pretreated MSCs with CXCR3 antagonist AMG-487 and p38 MAPK inhibitor SB203580 to confirm CXCR3-CXCL9 interaction and the role of CXCR3 in IL-1?-induced chemotaxis invasion and transendothelial migration. CONCLUSION:We found that IL-1? induces the expression of CXCR3 through p38 MAPK signaling and that IL-1? also enhances CXCL9 ligand secretion in HUVECs. These results indicated that IL-1? promotes the transendothelial migration of MSCs through CXCR3-CXCL9 axis. The implication of the finding could enhance the efficacy of MSCs homing to target sites.

Dataset Information

Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration.

Publications

Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration.

Similar Datasets

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