The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets

• Published in: Cellular immunology 2016-12, Vol.310, p.108-115
• Main Authors: Oezdemir, Alper Tunga, Oezguel Oezdemir, Rabia Bilge, Kirmaz, Cengiz, Sariboyaci, Ayla Eker, Uenal Halbutollari, Zehra Seda, Oezel, Ceren, Karaoz, Erdal
• Format: Article
• Language: English
• Subjects: CD4 T cell; Cell Differentiation; Cells, Cultured; Dental Pulp - pathology; Dinoprostone - metabolism; Forkhead Transcription Factors - metabolism; FoxP3; Gata3; GATA3 Transcription Factor - metabolism; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Humans; Immunomodulation; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Interleukin; Mesenchymal stem cell; Mesenchymal Stromal Cells - physiology; Paracrine Communication; Stat3; STAT3 Transcription Factor - metabolism; T-bet; T-Box Domain Proteins - metabolism; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2016.08.008

•hDP-MSCs significantly inhibited the proliferation of PHA-stimulated CD4+ T cells.•The CD4+Tbet+ and CD4+Gata3+ T cells were decreased by the hDP-MSCs.•The CD4+Stat3+ and CD4+CD25+FoxP3+ T cells were increased by the hDP-MSCs.•HGF may be important to plasticity of immunosuppressive regulatory Th17 cells. Mesenchymal stem cells (MSCs) have strong immunomodulatory properties, however these properties may show some differences according to the tissue type of their isolate. In this study we investigated the paracrine interactions between human DP derived MSCs (hDP-MSCs) and the CD4+ T helper cell subsets to establish their immunomodulatory mechanisms. We found that the CD4+-Tbet+ (Th1) and CD4+-Gata3+ (Th2) cells were suppressed by the hDP-MSCs, but the CD4+-Stat3+ (Th17) and CD4+-CD25+-FoxP3+ (Treg) cells were stimulated. The expressions of T cell specific cytokines interferon gamma (IFN-g), interleukin (IL)-4 and IL-17a decreased, but IL-10 and transforming growth factor beta-1 (TGF-b1) increased with the hDP-MSCs. The expressions of indoleamine-pyrrole 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), soluble human leukocyte antigen G (sHLA-G) derived from hDP-MSCs slightly increased, but hepatocyte growth factor (HGF) significantly increased in the co-culture groups. According to our findings, the hDP-MSCs can suppress the Th1 and Th2 subsets but stimulate the Th17 and Treg subsets. The Stat3 expression of Th17 cells may have been stimulated by the HGF, and thus the pro-inflammatory Th17 cells may have altered into the immunosuppressive regulatory Th17 cells. Further prospective studies are needed to confirm our findings.