CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells.
Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy.
STROMALab (Team 2), Université de Toulouse, EFS, INP-ENVT, INSERM U1031, UPS, 31042 Toulouse, France; EFS Pyrénées-Méditerranée, 31042 Toulouse, France.
Nicolas
N
Espagnolle
STROMALab (Team 2), Université de Toulouse, EFS, INP-ENVT, INSERM U1031, UPS, 31042 Toulouse, France; EFS Pyrénées-Méditerranée, 31042 Toulouse, France.
Adélie
A
Balguerie
STROMALab (Team 1), Université de Toulouse, CNRS ERL5311, EFS, INP-ENVT, INSERM U1031, UPS, 31042 Toulouse, France.
Emmanuelle
E
Arnaud
STROMALab (Team 2), Université de Toulouse, EFS, INP-ENVT, INSERM U1031, UPS, 31042 Toulouse, France; EFS Pyrénées-Méditerranée, 31042 Toulouse, France. Electronic address: luc.sensebe@efs.sante.fr.
Luc
L
Sensebé
STROMALab (Team 2), Université de Toulouse, EFS, INP-ENVT, INSERM U1031, UPS, 31042 Toulouse, France; EFS Pyrénées-Méditerranée, 31042 Toulouse, France. Electronic address: audrey.varin@efs.sante.fr.
Audrey
A
Varin
D002118:Calcium / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
D018799:Intercellular Adhesion Molecule-1; D002118:Calcium
CD54; bone marrow mesenchymal stromal cells; cell therapy; functional interaction; immunosuppression; indoleamine 2,3-dioxygenase; macrophages