Title: Mesenchymal Stromal Cells Impair the Differentiation of CD14++CD16-CD64+ Classical Monocytes into CD14++CD16+CD64++ Activate Monocytes
Abstract: Mesenchymal stromal cells (MSCs) possess immunomodulatory activity both in vitro and in vivo. However, little information is available about their function during the initiation of immunological responses through their interactions with monocytes. While many studies have shown that MSCs impair the differentiation of monocytes into dendritic cells and macrophages, there are few articles showing the interaction between MSCs and monocytes and none of them have addressed the question of monocyte subsets modulation. To better understand the mechanism behind the benefit of MSCs infusion for graft-versus-host treatment through monocytes involvement, we performed mixed leucocytes reactions (MLR) in the presence or absence of MSCs. After three or seven days, cultures were analyzed by flow cytometry using different approaches. MSCs induced changes in monocyte phenotype in a MLR. This alteration was accompanied by an increase in monocyte counting and in CD14 expression. MSCs induced monocyte alterations even without contact, although the parameters above were more pronounced with cell-cell contact. Moreover, the presence of MSCs impaired MHC I and II, CD11c, CCR5 expression and induced CD14 and CD64 expression on monocytes. These alterations were accompanied by a decrease in IL-1β and IL-6 production by these monocytes but no change was observed taking into account the phagocytosis capacity of these monocytes. Our results suggest that MSCs impair the differentiation of CD14++CD16-CD64+ classical monocytes into CD14++CD16+CD64++ activate monocytes, having a role even earlier than the differentiation of monocytes into dendritic cells and macrophages.