The immunomodulatory effects of mesenchymal stem cells (MSCs) are an important mediator of their therapeutic effects in stem cell therapy and regenerative medicine. The regulation mechanism of MSCs is orchestrated by several factors in both intrinsic and extrinsic events. Recent studies have shown that the dynamic expression of cytokines secreted from MSCs control T cell function and maturation by regulating the expression of FoxP3, which figures prominently in T cell differentiation. However, there is no evidence that placenta-derived mesenchymal stem cells (PD-MSCs) have strong immunomodulatory effects on T cell function and maturation via FoxP3 expression. Therefore, we compared the expression of FoxP3 in activated T cells isolated from peripheral blood and co-cultured with PD-MSCs or bone marrow-derived mesenchymal stem cells (BM-MSCs) and analyzed their effect on T cell proliferation and cytokine profiles. Additionally, we verified the immunomodulatory function of PD-MSCs by siRNA-mediated silencing of FoxP3. MSCs, including PD-MSCs and BM-MSCs, promoted differentiation of naive peripheral blood T cells into CD4+CD25+FoxP3+ regulatory T (Treg) cells. Intriguingly, the population of CD4+CD25+FoxP3+ Treg cells co-cultured with PD-MSCs was significantly expanded in comparison to those co-cultured with BM-MSCs or WI38 cells (p<0.05, p<0.001). Dynamic expression patterns of several cytokines, including anti- and pro-inflammatory cytokines and members of the transforming growth factor-beta (TGF-β) family secreted from PD-MSCs according to FoxP3 expression were observed. The results suggest that PD-MSCs have an immunomodulatory effect on T cells by regulating FoxP3 expression.
Organic acids have long been known for their beneficial effects on growth performance in domestic animals. However, their impact on immune responses against viral antigens in chickens is unclear. The present study aimed to investigate immunological parameters in broilers immunized with a H9N2 vaccine and/or fed a diet containing organic acids (citric, formic, and lactic acids). We allotted 1-day-old broilers into 4 groups: control (C), fed a diet supplemented with organic acids (O), administered a H9N2 vaccine (V), and fed a diet supplemented with organic acids and administered a H9N2 vaccine (OV). Blood and spleen samples were taken at 2, 7 and 14 d post vaccination (DPV). At 14 DPV, total and H9N2-specific IgG levels were significantly lower in the OV group than in the V group. However, it was intriguing to observe that at 2 DPV, the percentage of CD4+CD25+ T cells was significantly higher in the OV group than in the other groups, indicating the potential induction of regulatory T cells by organic acids. In contrast, at 2 DPV, the percentage of CD4+CD28+ T cells were significantly lower in the OV group than in the other groups, suggesting that CD28 molecules are down-regulated by the treatment. The expression of CD28 on CD4+ T cells, up-regulated by the stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (Iono), was inhibited upon organic acid treatment in OV group. In addition, the proliferation of lymphocytes, stimulated with formalin-inactivated H9N2, was significantly higher in the V group than in the OV group. Alpha 1-acid glycoprotein (AGP) production was significantly lower in the OV group than in the V group, suggesting that the organic acids inhibited the inflammation caused by the vaccination. Overall, induction of regulatory CD4+CD25+ T cells, coinciding with the decrease of H9N2-specific antibodies, was observed in broilers fed organic acids.
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