Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion

• Published in: Experimental hematology Vol. 40; no. 9; pp. 761 - 770
• Main Authors: Qu, Xuebin, Liu, Xingxia, Cheng, Kai, Yang, Rongcun, Zhao, Robert C.H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-09-2012
• Subjects: Advanced Basic Science; Animals; Blotting, Western; Cell Differentiation; Cells, Cultured; Coculture Techniques; Flow Cytometry; Hematology, Oncology and Palliative Medicine; Interleukin-10 - genetics; Interleukin-10 - metabolism; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred BALB C; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; STAT3 Transcription Factor - metabolism; STAT5 Transcription Factor - metabolism; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - metabolism; Th17 Cells - metabolism
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2012.05.006

Recent findings indicate that mesenchymal stem cells (MSCs) may act as a regulator of Th17 cell differentiation, however, the underlying mechanism is still under debate. To investigate the underlying mechanisms of MSCs' regulatory effect, mouse bone marrow–derived MSCs were cocultured with mouse CD4+ CD25low CD44low CD62Lhigh T cells in vitro, and the proportion of induced Th17 cells, cytokines secretion, and transcription factors expression were examined by flow cytometry, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and Western blotting. For the first time, our results showed that bone marrow–derived MSCs were able to inhibit Th17 cell differentiation via interleukin (IL)-10 secretion as the Th17 cell proportion was significantly regained when IL-10 was neutralized, or expression of IL-10 by bone marrow–derived MSCs was downregulated by RNA interference technique. Furthermore, IL-10 may suppress expression of Rorγt, the key transcription factor for Th17 cells, both by activating suppressor of cytokine signaling 3 through signal transducers and activators of transcription 5 phosphorylation, and decreasing signal transducers and activators of transcription 3 binding, which is at the promoter of Ror γ t . Thus, our results demonstrate the inhibitory effect of MSCs on Th17 cells differentiation, and suggest increased IL-10 secretion might be the key factor.