Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Figure 4 Mesenchymal stem cell immunosuppression of adaptive immune cells. In the context of B cells, mesenchymal stem cells (MSCs) inhibit various facets of B cells activity, including activation, proliferation, chemokine receptor expression, and differentiation to becoming antibody-secreting plasma cells. Unknown soluble factors and PD-1/PD-L1 ligation mediate these effects of MSCs on B cells. MSC have been shown to induce NO in response to inflammatory cytokine detection to suppress CD8+ T cell proliferation, cytokine production, and cytotoxicity. In response to activation in specific cytokine milieus, CD4+ T cells can differentiate into numerous effector populations. MSCs produce soluble factors (NO, TGF-B, HGF, PGE2, truncated CCL-2, and IL-10) and membrane-bound molecules (PD-1 ligation) to achieve suppression of CD4+ T cell proliferation and the polarization of CD4+ T cells towards TH1 and TH17 cells. MSCs favor the development of TH2 and anti-inflammatory Treg populations.