Immunomodulatory effects of dental pulp stem cells on lymphocytes and monocytes from patients with rheumatoid arthritis.

OBJECTIVES

To investigate the immunomodulatory effects of dental pulp stem cells (DPSCs) on lymphocytes and monocytes from rheumatoid arthritis (RA) patients unresponsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).

METHODS

Peripheral blood lymphocytes and monocytes were isolated from 12 RA patients unresponsive to csDMARDs. Lymphocytes were activated using anti-CD3/CD28 beads or with CpG ODN 2006, and monocytes with LPS. After 48 hours of co-culture with DPSCs, the expression of 7 immune checkpoints on DPSCs was analysed by flow-cytometry, and 17 cytokines were quantified in the supernatants.

RESULTS

Co-culture of DPSCs with CD3/CD28-activated lymphocytes or LPS-activated monocytes increased the expression of PD-L1, PD-L2, CD155, and Galectin-9 on DPSCs. In contrast, lymphocytes activated with ODN 2006 did not alter immune checkpoint expression. CD80, CD86, and 4-1BBL expression was not induced under any condition. Co-culture with DPSCs reduced levels of sFas-L, IFNγ, sIL-6RA, MIP-1β, TNFα in supernatants of CD3/CD28-activated lymphocytes; and BAFF, sFas-L, IL-1β, sIL-6RA, IL-9, IL-17A, IL-18, IL-23, M-CSF, perforin, TNFα in supernatants of LPS-activated monocytes. IL-6 and IP-10 levels increased in all experimental conditions, while IL-9 increased in ODN 2006- and CD3/CD28-stimulated lymphocyte cultures. DPSCs showed differential effects depending on the activation status of lymphocytes and monocytes.

CONCLUSIONS

The overexpression of inhibitory immune checkpoints by DPSCs may contribute to their immunomodulatory effects. DPSCs modulated a broader range of cytokines in monocyte supernatants compared to lymphocytes.