New insights into mesenchymal stromal cell-mediated T-cell suppression through galectins

Abstract

In recent years, a large number of studies have contributed to our understanding of the immunosuppressive mechanisms used by mesenchymal stromal cells (MSC). These include the expression of indoleamine 2,3-dioxygenase (IDO) and the production of soluble immunosuppressive factors, such as, interleukin-10 (IL-10), transforming growth factor β (TGF-β) and prostaglandin E2 (PGE2). However, whether these factors represent the only triggers involved in immunosuppression is not clear. Indeed, adding IDO inhibitor or neutralizing antibodies against IL-10 and TGF-β to mixed lymphocyte reactions failed to prevent T-cell suppression by MSC, suggesting that there is either redundancy in the mechanisms of immunosuppression or the involvement of other factors yet to be described. Galectins, a family of β-galactoside binding proteins, now emerge as a main regulator of MSC immunosuppressive function. Galectin-1 and galectin-3 are constitutively expressed and secreted by human bone marrow MSC. Inhibition of galectin-1 and galectin-3 gene expression with small interfering RNAs abrogated the suppressive effect of MSC on allogeneic T cells. An increase in our understanding of MSC suppressor mechanisms will offer an insight into the use of these cells in human therapy such as the treatment of graft-versus-host disease, a severe complication after haematopoietic stem cell transplantation.