Fig. 5.

Probiotics showed modulatory effects on MSCs activity. The N-MSCs group reduced the serum levels of IL-4, IL-17, and IFN-ɣ compared to the P–C group. The reduction was found to be significant in the case of IL-4 and IFN-ɣ. Compared to the P–C group, in the R-MSCs group, the reduction in the serum level of the mentioned cytokines had the same pattern as in the N-MSCs group, but the intensity of the diminish was more noticeable. In the group which received L. delbrueckii-pretreated MSCs, a significant reduction was found in the serum level of IL-4, accompanied by a nonsignificant reduction in the IL-17, with no change in the level of IFN-ɣ, when compared to the P–C group. On the other hand, compared with the P–C group, despite the significant decrease in the serum level of IL-4, the DR-MSCs group exhibited stimulant effects for IFN-ɣ and IL-17, as inflammatory inducers, which not verified our hypothesis. Actually, in contrast to MSCs pretreated by L. rhamnosus or L. delbrueckii, a mixed suspension of probiotics provoked MSCs to increase inflammatory cytokines. In addition, TGF-β was significantly found to be enhanced in MSC-treated groups. It was the highest in the sera of the R-MSCs group, while it was the lowest in the sera of the P–C group. These findings revealed that bacteria can have a vital role in modulating MSC–host immunocytes interactions in the systemic immune system. Tukey’s multiple comparisons was used to determine the relationship between the variables means. N–C: Negative Control (Healthy mice treated with PBS); P–C: Positive Control (Pristane-immunized mice treated with PBS); N-MSCs (Naïve MSCs without any interventions); R-MSCs: MSCs exposed to lactobacillus rhamnosus; D-MSCs: MSCs exposed to lactobacillus delbrueckii; DR-MSCs: MSCs exposed to a mixture of lactobacillus rhamnosus and delbrueckii. Data were presented as Mean ± Standard Error of the Mean (SEM). P values of ≤ 0.05 were considered significant. (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001)