Role of toll-like receptors on placental derived mesenchymal stem cells and their protection from natural killer cells

Abstract NK cells are major effector cells of the innate immunity. It is not clear that how MSCs can escape allogeneic NK cells killing and survival. The study included human placenta from women who were healthy and had full-term naturally-delivered male newborns (n = 5). Peripheral blood samples were obtained from healthy voluntary donors (n = 5). Karyotype analysis was carried out to determine the origin of the MSCs. Expression of TLR1-TLR10 was assessed by PCR. IL-1beta, IL-6 and IL-8 in MSCs were primed by Toll-like receptor agonists. MSCs primed by different Toll-like receptor (TLR) agonists and NK cells activated with IL-2 were co-cultured. CD107α were analyzed by flow cytometry. The NK cell-activating receptors NKp30, NKG2D, and DNAM-1 were analyzed by FCM. Also the levels of IL-10, IFN-γ and TNF-αwere evaluated by ELISA. Karyotype analyses indicated that cells were derived from the maternal matrix. The expression of TLR3 and 4 was higher when compared to the other molecules. In CD107α degranulation assay, MSCs primed by poly (I: C) and LPS reduced cytotoxic granules with significant differences (P < 0.05) when compared to the positive group. The NK cell-activating receptors NKp30, NKG2D, and DNAM-1 were high expression in activated NK group, but were inhibited during co-culture with MSC and primed MSC. The higher levels of IFN-γ, IL-10 and TNF-αwhich augment MSC suppressive function were secreted in B,C and D group. TLR3 and 4-primed MSCs reduced cytotoxicity of NK cells and protected from NK cell killing.