CD54-mediated interaction with pro-inflammatory macrophages increases the immunosuppresive 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 between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MФ) 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 new perspectives for MSC-based cell therapy. Human bone-marrow derived mesenchymal stromal cells were co-cultivated with pro (M1MФ) or anti (M2MФ) -inflammatory macrophages. After 24h of co-culture, cells were detached and MSCs and MФ were magnetically separated based on the CD45 expression using the AutoMACS pro separator.