Department of Gastroenterology, West China Hospital of Sichuan University, 37 Guoxue Street, Chengdu 610041, China.
Immunol Lett. 2013 Nov-Dec;156(1-2):23-9. doi: 10.1016/j.imlet.2013.09.006. Epub 2013 Sep 20.
To elucidate the immunomodulatory functions of colonic mesenchymal stem cells (MSCs) in the colonic mucosal immune system.
The colonic MSCs were isolated, enriched and expanded. The immunosuppressive role of colonic MSCs on activated T cells was evaluated. The cell cycle progression of T cells and the expression of FoxP3+ T cells were assessed by fluorescence-activated cell sorting (FACS). The levels of cytokines and PGE2 were measured by ELISA.
Mouse colonic MSCs can inhibit the proliferation of activated T cells by arresting cells in G0/G1 phase, induce the expression of CD4+CD25+Foxp3+ T cells (8.05%±0.49% in transwell culture vs 8.45%±0.64% in direct contact culture vs 4.30%±0.28% in control, p<0.05), downregulate the levels of the cytokines TNF-α and IFN-γ, and increase the production of IL-10 (p<0.05). The data obtained from transwell culture and direct contact culture showed no difference (p>0.05). PGE2 level was increased when T cells were cultured with colonic MSCs (385.10±19.45 ng/l in transwell culture vs 387.91±19.85 ng/l in direct contact culture vs 276.21±25.49 ng/l in control, p<0.05). Blocking PGE2 partially reversed the immunosuppression of MSCs on activated T cells proliferation (p<0.05).
Colonic MSCs have the same immunosuppressive property as other MSCs. They performed their functions partially through secreting soluble factor PGE2. The characterization of these colonic MSCs may be helpful for studying the involvement of stromal cell compartment in colon diseases.
阐明结肠间充质干细胞(MSCs)在结肠黏膜免疫系统中的免疫调节功能。
分离、富集和扩增结肠 MSCs。评估结肠 MSCs 对活化 T 细胞的免疫抑制作用。通过流式细胞术(FACS)评估 T 细胞的细胞周期进程和 FoxP3+T 细胞的表达。通过 ELISA 测定细胞因子和 PGE2 的水平。
小鼠结肠 MSCs 可通过将细胞阻滞在 G0/G1 期来抑制活化 T 细胞的增殖,诱导 CD4+CD25+Foxp3+T 细胞的表达(转染培养中为 8.05%±0.49%,直接接触培养中为 8.45%±0.64%,对照组中为 4.30%±0.28%,p<0.05),下调 TNF-α和 IFN-γ细胞因子的水平,并增加 IL-10 的产生(p<0.05)。转染培养和直接接触培养获得的数据无差异(p>0.05)。当 T 细胞与结肠 MSCs 共培养时,PGE2 水平增加(转染培养中为 385.10±19.45ng/l,直接接触培养中为 387.91±19.85ng/l,对照组中为 276.21±25.49ng/l,p<0.05)。阻断 PGE2 部分逆转了 MSCs 对活化 T 细胞增殖的免疫抑制作用(p<0.05)。
结肠 MSCs 具有与其他 MSCs 相同的免疫抑制特性。它们通过分泌可溶性因子 PGE2 部分发挥其功能。这些结肠 MSCs 的特征可能有助于研究基质细胞在结肠疾病中的作用。