MSCs down-modulate in vitro pro-inflammatory responses. Using in vitro assays, BMSCs have been shown to interact with immune effector cells either through direct contact or through the induction of paracrine immunomodulatory soluble factors, such as galectin-1, HO-1, HLA-G5, hepatocyte growth factor, IL-10, IDO, PGE₂, and TGF-β1. Specifically, BMSCs inhibit monocyte (Mo) differentiation into DCs as well as DC activation and maturation; inhibit naive T-cell activation, Th1 proliferation, and cytokine production (TNF-α and IFN-γ); inhibit B-cell proliferation and differentiation into plasma cells; and inhibit NK cell proliferation, cytotoxicity, and IFN-γ production. In contrast, BMSCs induce Treg cells. Soluble factors, including IL-1β, IFN-γ, TNF-α, and TLR ligands, have been shown to provide necessary signals for in vitro MSC activation.