Mesenchymal stromal cells impair the differentiation of CD14 ~(++) CD16 ~- CD64 ~+ classical monocytes into CD14 ~(++) CD16 ~+ CD64 ~(++) activate monocytes

摘要

Mesenchymal stromal cells (MSC) possess immunomodulatory activity both in vitro and in vivo. However, little information is available regarding their function during the initiation of immunologic responses through their interactions with monocytes. While many studies have shown that MSC impair the differentiation of monocytes into dendritic cells and macrophages, there are few articles showing the interaction between MSC and monocytes and none of them has addressed the question of monocyte subset modulation. Methods. To understand better the mechanism behind the benefit of MSC infusion for graft-versus-host treatment through monocyte involvement, we performed mixed leucocyte reactions (MLR) in the presence and absence of MSC. After 3 and 7 days, cultures were analyzed by flow cytometry using different approaches. Results. MSC induced changes in monocyte phenotype in an MLR. This alteration was accompanied by an increase in monocyte counting and CD14 expression. MSC induced monocyte alterations even without contact, although the parameters above were more pronounced with cellcell contact. Moreover, the presence of MSC impaired major histocompatibility complex (MHC) I and II, CD11c and CCR5 expression and induced CD14 and CD64 expression on monocytes. These alterations were accompanied by a decrease in interleukin (IL)-1β and IL-6 production by these monocytes, but no change was observed taking into account the phagocytosis capacity of these monocytes. Conclusions. Our results suggest that MSC impair the differentiation of CD14 ~(++) CD16 ~- CD64 ~+ classical monocytes into CD14 ~(++) CD16 ~+ CD64 ~(++) activated monocytes, having an even earlier role than the differentiation of monocytes into dendritic cells and macrophages.