Adipogenic differentiation alters the immunoregulatory property of mesenchymal stem cells through BAFF secretion

Abstract

Although it has been widely demonstrated that mesenchymal stem cells (MSCs) exert potent immunosuppressive effect, there is little information as to whether adipogenic-differentiated MSCs (adi-MSCs) share the same property. Here, adi-MSCs enhanced alloantigen or mitogen-stimulated lymphocyte proliferation, whereas undifferentiated MSCs (ud-MSCs) inhibited the proliferation. Transwell experiment showed that the stimulatory effect of adi-MSCs was cell–cell contact-independent, and required soluble factors. Furthermore, the supernatant of cultured adi-MSCs could effectively costimulate T and B-lymphocyte proliferation and activation in the presence of anti-CD3 and anti-mu chain treatment, respectively. Production of cytokines interferon-gamma and tumor necrosis factor-alpha by T cells, and Ig secretion by B cells also were increased by the supernatant of cultured adi-MSCs. Mechanism conducted showed that the mRNA and protein expression of costimulatory molecule B-cell activating factor (BAFF) was upregulated, and soluble BAFF was secreted in MSCs after adipogenic differentiation. By blocking the BAFF molecule with specific monoclonal antibody in the culture, T and B-lymphocyte proliferation and activation was stimulated by adi-MSCs or the supernatants were greatly reduced. In conclusion, adipogenic differentiation may alter the immunoregulatory property of MSCs, leading to stimulation of lymphocytes response. The BAFF molecule secreted by the adi-MSCs was responsible for this event.