Gene expression profile reveals that STAT2 is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells

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• 作者：TacGhee Yi^a ; ^b ; ^d ; ¹ ; Dong-Seok Lee^c ; ¹ ; Myung-Shin Jeon^a ; ^b ; ^d ; Sung Won Kwon^e ; Sun U. Song^a ; ^c ; ^d ; ^{sunuksong@inha.ac.kr}
• 关键词：MSCs ; mesenchymal stem cells ; IFN-纬 ; interferon-纬 ; TNF-伪 ; tumor necrosis factor-伪 ; TGF-尾 ; transforming growth factor-尾 ; IDO ; indoleamine 2 ; 3-dioxygenase ; DCs ; dendritic cells ; NK ; natural killer ; GVHD ; graft-versus-host disease ; NO ; nitric oxide ; PH
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：15 April, 2012
• 卷：497
• 期：2
• 页码：131-139
• 文件大小：846 K

摘要

Emerging evidence of the potent immunosuppressive activity of mesenchymal stem cells (MSCs) by modulation of both innate and adaptive immune responses enables MSCs to be developed as a promising therapeutic modality for immune-related or inflammatory diseases. However, it is not clearly understood how MSCs exert their immunosuppressive effects on immune cells under inflammatory conditions. Using human bone marrow (BM)-derived clonal MSCs (hcMSCs), we obtained and analyzed a differentially expressed gene profile when stimulated with the inflammatory cytokines interferon-纬 (IFN-纬) and tumor necrosis factor-伪 (TNF-伪) to find novel candidate factors responsible for MSC immunomodulation. Microarray analysis showed that 5650 genes were upregulated and 5862 genes were downregulated with the cutoff of 2-fold expression change. Among these, the ICOSLG and STAT2 genes were drastically upregulated 173-fold and 154-fold, respectively. Reverse transcription-polymerase chain reaction analysis confirmed the microarray data. To evaluate whether their increased expression is related to MSC-mediated immunosuppression, siRNA-induced ICOSLG- or STAT2-knockdown hcMSCs were assessed for their T cell suppressive activity. We demonstrated that STAT2 but not ICOSLG is functionally involved in the immunosuppressive activity of hcMSCs as a novel regulator under inflammatory conditions. Gene ontology and pathway analyses further support the immunomodulatory function of hcMSCs when inflammatory stimulation was provided. Taken together, this study provides an informative genome-wide gene expression profile and molecular evidence for understanding the mechanisms underlying the modulation of immune cells by human BM-derived MSCs under inflammatory conditions.