Regulation of MHC Class II Expression and Antigen Processing in Murine and Human Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSC) possess immunosuppressive properties, yet when treated with IFN- they acquire APC func-tions. To gain insight into MSC immune plasticity, we explored signaling pathways induced by IFN- required for MHC class II (MHC II)-dependent Ag presentation. IFN--induced MHC II expression in mouse MSC was enhanced by high cell density or serum deprivation and suppressed by TGF-. This process was regulated by the activity of the type IV CIITA promoter inde-pendently of STAT1 activation and the induction of the IFN regulatory factor 1-dependent B7H1/PD-L1 encoding gene. The absence of direct correlation with the cell cycle suggested that cellular connectivity modulates IFN- responsiveness for MHC II expression in mouse MSC. TGF- signaling in mouse MSC involved ALK5 and ALK1 TGF-RI, leading to the phosphorylation of Smad2/Smad3 and Smad1/Smad5/Smad8. An opposite effect was observed in human MSC where IFN--induced MHC II expression occurred at the highest levels in low-density cultures; however, TGF- reduced IFN--induced MHC II expression and its signaling was similar as in mouse MSC. This suggests that the IFN--induced APC features of MSC can be modulated by TGF-, serum factors, and cell density in vitro, although not in the same way in mouse and human MSC, via their convergent effects on CIITA expression. The Journal of Immunology, 2007, 179: 1549–1558. M esenchymal stromal cells (MSC)4 are bone marrow-derived mesenchymal progenitors thought to give riseto cells that constitute the hemopoietic microenviron-ment. MSC are classically expanded in vitro from the plastic-ad-herent cell population from bone marrow aspirates. MSC can serv