Inhibitory effects of tolerogenic probiotics on migratory potential of lupus patient-derived DCs

Abstract

Objectives: The present in vitro study aimed to evaluate whether Lactobacillus delbrueckii and Lactobacillus rhamnosus treatments can induce regulatory phenotype, together with modulating the expression of chemokine receptors (CRs) in dendritic cells (DCs). The CRs of DCs have been found to be involved in the pathogenesis of Systemic lupus erythematosus (SLE) through directing recruitment and migration of immune cells.

Materials and methods: In brief, monocytes of patients with SLE and healthy donors were isolated and differentiated to regulatory or inflammatory mature DCs through treatment with L. delbrueckii, L. rhamnosus, mixed probiotics, and LPS.

Results: FACScan analysis showed that the expression of CRs including CXCR3, CCR5, CCR4, and CCR3, was significantly reduced in all probiotic-treated groups of SLE and healthy (control) donors when compared with the LPS treated group.

Conclusion: The results demonstrated that tolerogenic probiotics could prevent or decrease the expression of inflammatory CRs on the surface of tolerogenic DCs during the maturation process.

Keywords: Chemokine receptor; Lactobacillus Delbrueckii; Lactobacillus Rhamnosus; Systemic lupus – erythematosus; Tolerogenic dendritic cell.

Figure 1

DC uptake assay results. Results of IDCs Ability to uptake FITC-dextran dye. The results showed that IDCs were able to pick up the dye after incubation. Histogram and dot plot of flow cytometry results demonstrated 95.3% and 95.4% of IDCs pick up the dye, respectively

Figure 2

Flow cytometry results. Results of chemokine receptor expression (CXCR3, CCR5, CCR4, and CCR3) in treated MDCs of SLE and healthy donors. (CXCR3): Expression of CXCR3 was decreased in MDC-DEL, MDC-RAM, and MDC-MIX groups of both patients and healthy donors. cMDC-DEL, cMDC-RAM, and cMDC-MIX along with cMDC-LPS have shown lower significant expression compared with pMDC- LPS. (P<0.0004). (CCR5): In all probiotics treated groups in both healthy and SLE donors significant reduction was observed compared with LPS groups (P<0.0001). (CCR4): In all probiotics treated groups in both healthy and SLE donors reduction was observed compared with LPS groups but not significantly. (CCR3): Expression in probiotics treated groups was significant and lower than LPS treated groups, also lower significance was observed in pMDC-DEL and pMDC-MIX in comparison with corresponding sub-groups of healthy donors (P<0.0001)