Unveiling the role of TNF-α in mesenchymal stromal cell-mediated immunosuppression

Mesenchymal stromal cells (MSCs) are multipotent progenitors of mesodermal origin that not only differentiate into osteoblasts, chondrocytes, connective stromal cells, and adipocytes, but also exert immunoregulatory activities, usually induced by soluble molecules released during the cross-talk between MSCs and their target immune cell populations. In this issue of the European Journal of Immunology, Dorronsoro et al. [Eur. J. Immunol. 2014. 44: 480-488] demonstrate for the first time that TNF-α released by activated T cells confers immunosuppressive properties upon MSCs by binding to TNF-R1 and activating the NF-kB pathway. Such findings may improve our knowledge of the mechanisms underlying the reported efficacy of human MSCs administered locally or systemically to patients with autoimmune/inflammatory disorders, such as Crohn's disease and graft versus host disease, as discussed in this commentary.