Dataset Information

Recruitment of MAIT Cells to the Intervillous Space of the Placenta by Placenta-Derived Chemokines.

ABSTRACT: The intervillous space of the placenta is a part of the fetal-maternal interface, where maternal blood enters to provide nutrients and gas exchange. Little is known about the maternal immune cells at this site, which are in direct contact with fetal tissues. We have characterized the T cell composition and chemokine profile in paired intervillous and peripheral blood samples from healthy mothers giving birth following term pregnancies. Mucosal-associated invariant T (MAIT) cells and effector memory (EM) T cells were enriched in the intervillous blood compared to peripheral blood, suggesting that MAIT cells and other EM T cells home to the placenta during pregnancy. Furthermore, pregnant women had lower proportions of peripheral blood MAIT cells compared to non-pregnant women. The levels of several chemokines were significantly higher in intervillous compared to peripheral blood, including macrophage migration inhibitory factor (MIF), CXCL10, and CCL25, whereas CCL21, CCL27 and CXCL12 were lower. Migration assays showed that MAIT cells and EM T cells migrated toward conditioned medium from placental explants. A multivariate factor analysis indicated that high levels of MIF and CCL25 were associated with high proportions of MAIT cells in intervillous blood. Blocking of MIF or a combination of MIF, CCL25, and CCL20 in migration assays inhibited MAIT cell migration toward placenta conditioned medium. Finally, MAIT cells showed migratory capacities toward recombinant MIF. Together, these findings indicate that term placental tissues attract MAIT cells, and that this effect is at least partly mediated by MIF.

SUBMITTER: Solders M

PROVIDER: S-EPMC6563723 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Recruitment of MAIT Cells to the Intervillous Space of the Placenta by Placenta-Derived Chemokines.

Solders Martin M Gorchs Laia L Tiblad Eleonor E Gidlöf Sebastian S Leeansyah Edwin E Dias Joana J Sandberg Johan K JK Magalhaes Isabelle I Lundell Anna-Carin AC Kaipe Helen H

Frontiers in immunology 20190606

The intervillous space of the placenta is a part of the fetal-maternal interface, where maternal blood enters to provide nutrients and gas exchange. Little is known about the maternal immune cells at this site, which are in direct contact with fetal tissues. We have characterized the T cell composition and chemokine profile in paired intervillous and peripheral blood samples from healthy mothers giving birth following term pregnancies. Mucosal-associated invariant T (MAIT) cells and effector mem ...[more]

PMID: 31244846

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Project description:BackgroundThe therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to humoral factors such as growth factors, cytokines, and chemokines. Human term placental tissue-derived MSCs (PlaMSCs), or conditioned medium left over from cultures of these cells, have been reported to enhance angiogenesis. Recently, the exosome, which can transport a diverse suite of macromolecules, has gained attention as a novel intercellular communication tool. However, the potential role of the exosome in PlaMSC therapeutic action is not well understood. The purpose of this study was to evaluate PlaMSC-derived exosome angiogenesis promotion in vitro and in vivo.MethodsMSCs were isolated from human term placental tissue by enzymatic digestion. Conditioned medium was collected after 48-h incubation in serum-free medium (PlaMSC-CM). Angiogenic factors present in PlaMSC-CM were screened by a growth factor array. Exosomes were prepared by ultracentrifugation of PlaMSC-CM, and confirmed by transmission electron microscopy, dynamic light scattering, and western blot analyses. The proangiogenic activity of PlaMSC-derived exosomes (PlaMSC-exo) was assessed using an endothelial tube formation assay, a cell migration assay, and reverse transcription-PCR analysis. The in-vivo angiogenic activity of PlaMSC-exo was evaluated using a murine auricle ischemic injury model.ResultsPlaMSC-CM contained both angiogenic and angiostatic factors, which enhanced endothelial tube formation. PlaMSC-exo were incorporated into endothelial cells; these exosomes stimulated both endothelial tube formation and migration, and enhanced angiogenesis-related gene expression. Laser Doppler blood flow analysis showed that PlaMSC-exo infusion also enhanced angiogenesis in an in-vivo murine auricle ischemic injury model.ConclusionsPlaMSC-exo enhanced angiogenesis in vitro and in vivo, suggesting that exosomes play a role in the proangiogenic activity of PlaMSCs. PlaMSC-exo may be a novel therapeutic approach for treating ischemic diseases.

Project description:DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34(+) hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-alpha or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34(+) HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3alpha, but also to MIP-1alpha and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-alpha, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3beta. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3alpha and MIP-3beta, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3beta responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3beta is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3alpha mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3beta mRNA specifically in T cell-rich areas, suggests a role for MIP-3alpha/CCR6 in recruitment of immature DCs at site of injury and for MIP-3beta/CCR7 in accumulation of antigen-loaded mature DCs in T cell-rich areas.

Dataset Information

Recruitment of MAIT Cells to the Intervillous Space of the Placenta by Placenta-Derived Chemokines.

Publications

Recruitment of MAIT Cells to the Intervillous Space of the Placenta by Placenta-Derived Chemokines.

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