Rapid paper
Immunomodulatory effects of dental pulp stem cells on lymphocytes and monocytes from patients with rheumatoid arthritis
A. Rossi1, G. Ferrari2, V. Galli3, M. Bonacini4, G. Carnevale5, A. Pisciotta6, R. Di Tinco7, M. Catanoso8, F. Brandolino9, C. Galluzzo10, A. Zerbini11, C. Salvarani12, S. Croci13
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy.
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy.
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy.
- Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena; and Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
- Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
CER18834
2025 Vol.43, N°5
PI 0809, PF 0814
Rapid paper
Free to view
(click on article PDF icon to read the article)
PMID: 40338061 [PubMed]
Received: 14/04/2025
Accepted : 29/04/2025
In Press: 08/05/2025
Published: 08/05/2025
Abstract
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.
