CD39-mediated IL-6 expression in mesenchymal stromal cells inhibiting T-cell activation

초록

Mesenchymal stem cells (MSCs) are well-known for their capacity for pluripotent differentiation and their wide range of immunomodulatory abilities, particularly in inhibiting T-cell responses. Among the factors involved in MSC-mediated immune regulation, CD39, a surface protein involved in adenosine production, has been extensively studied. However, the role of CD39 in MSCs has not yet been fully explored. In this study, we investigated the role of CD39 in mouse bone marrow-derived MSCs in regulating T cells. Initially, we observed that the expression level of CD39 differed among MSCs. Secondly, MSCs with high CD39 expression exhibited a greater capacity to inhibit T-cell proliferation and IFN-? production while increasing IL-2 and IL-6 expression. Additionally, a decrease in CD122 (IL-2R?) expression in T cells was observed. Thirdly, the level of CD39 expression was found to be involved in IL-6 expression in MSCs. Administering an IL-6 neutralizing antibody restored T-cell proliferation in the presence of MSCs. Conversely, treating with recombinant IL-6 protein increased MSC-mediated inhibition of T-cell proliferation. Fourthly, the increased IL-2 and decreased CD122 expression by MSCs were recovered by the IL-6 neutralizing antibody. In conclusion, these findings suggest that CD39 in MSCs is involved in IL-6 expression, which may inhibit IL-2 receptor expression and suppress T-cell proliferation. These results may underscore the importance of CD39 in MSCs as a critical regulator of T-cell responses and highlight CD39's potential as a biomarker for predicting MSC-mediated immunosuppression.